研究者業績
基本情報
経歴
16-
2020年2月 - 現在
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2018年9月 - 2020年1月
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2017年4月 - 2018年8月
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2017年1月 - 2018年8月
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2014年7月 - 2017年3月
学歴
2-
2000年4月 - 2004年3月
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1987年4月 - 1993年3月
委員歴
1-
2019年4月 - 現在
論文
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FEBS open bio 2024年2月15日Acute lung injury (ALI), which occurs in association with sepsis, trauma, and coronavirus disease 2019 (COVID-19), is a serious clinical condition with high mortality. Excessive platelet-leukocyte aggregate (PLA) formation promotes neutrophil extracellular trap (NET) release and thrombosis, which are involved in various diseases, including ALI. Macrophage-1 antigen (Mac-1, CD11b/CD18), which is expressed on the surface of leukocytes, is known to promote NET formation. This study aimed to elucidate the role of Mac-1 in extracellular histone-induced ALI. Exogenous histones were administered to Mac-1-deficient mice and wild-type (WT) mice with or without neutrophil or platelet depletion, and several parameters were investigated 1 h after histone injection. Depletion of neutrophils or platelets improved survival time and macroscopic and microscopic properties of lung tissues, and decreased platelet-leukocyte formation and plasma myeloperoxidase levels. These improvements were also observed in Mac-1-/- mice. NET formation in Mac-1-/- bone marrow neutrophils (BMNs) was significantly lower than that in WT BMNs. In conclusion, our findings suggest that Mac-1 is associated with exacerbation of histone-induced ALI and the promotion of NET formation in the presence of activated platelets.
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BMJ open 14(1) e076962 2024年1月24日INTRODUCTION: Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population. METHODS AND ANALYSIS: This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse. ETHICS AND DISSEMINATION: The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: jRCTs041220126.
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Internal medicine (Tokyo, Japan) 2023年9月29日Objective The objective of this study was to estimate the humoral immune response evaluated by immunoglobulin G (IgG) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-IgG) following the third mRNA COVID-19 vaccination in patients with kidney disease who received immunosuppressive treatment. Methods The primary outcome was RBD-IgG levels after the third SARS-CoV-2 vaccination. The primary comparison was the RBD-IgG levels between patients with kidney disease who received immunosuppressive treatment (n=124) and those who did not (n=33). Results The RBD-IgG levels were significantly lower in the patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. The RBD-IgG levels were lower in patients treated with glucocorticoid monotherapy than in those who did not receive immunosuppressive treatment. Even in patients who received ≤ 5 mg prednisolone, the RBD-IgG levels were significantly lower. Nine of the 10 patients who received rituximab within one year before the first vaccination did not experience seroconversion after the third vaccination. Meanwhile, all nine patients who received rituximab only after the second vaccination experienced seroconversion, even if B cell recovery was insufficient. Patients treated with mycophenolate mofetil plus glucocorticoid plus belimumab had significantly lower RBD-IgG levels than those treated with mycophenolate mofetil plus glucocorticoid. Conclusions The RBD-IgG levels were lower in patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. Low-dose glucocorticoid monotherapy affected the humoral immune response following the third mRNA COVID-19 vaccination.
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Biochemical and biophysical research communications 678 179-185 2023年8月23日Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca2+-dependent cross-linking enzyme in blood, mediates fibrin deposition. As another isozyme, transglutaminase 2 (TG2) has a catalytic activity distributing in most tissues. Herein, we investigated whether TG2 promotes fibrin deposition and mediates the adhesion of platelets to ECs in histone-induced acute lung injury (ALI). We evaluated the lung histology and the adhesion of platelets to endothelial cells (ECs) after injecting histones to wild-type (WT) C57BL/6J and TG2 knockout (TG2-/-) mice, and administered a TG2 inhibitor (NC9) to WT mice. Pulmonary haemorrhage was more severe in TG2-/- mice than that in WT mice. The area of fibrin deposition and the proportion of CD41+CD31+ cells were lower in TG2-/- mice than in WT mice. Pre-treatment of NC9 decreased the area of fibrin deposition and the proportion of CD41+CD31+ cells in WT mice. These results suggest that TG2 prevents from pulmonary haemorrhage in ALI by promoting the adhesion of platelets to ECs and the fibrin deposition.
MISC
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NEPHROLOGY 21 110-110 2016年9月
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NEPHROLOGY 21 114-115 2016年9月
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JOURNAL OF RHEUMATOLOGY 42(10) 1853-1860 2015年10月 査読有りObjective. The diagnostic values of antiproteinase 3 and antimyeloperoxidase tests using antineutrophil cytoplasmic antibodies (ANCA) are well established. Our study determined whether an increase in ANCA level was a predictor of disease flareup. Methods. Our study included 126 patients with ANCA-associated renal vasculitis treated at 9 nephrology centers in Japan. The relationship between increased ANCA levels and relapse was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors. The outcome of interest was the time from remission to first relapse. Results. During the observation period [median 41 mos, interquartile range (IQR) 23-66 mos], 118 patients (95.8%) achieved remission at least once. After achieving remission, 34 patients relapsed (21.7%). Time-dependent multivariate Cox regression models revealed that lung involvement (adjusted HR 2.29, 95% CI 1.13-4.65, p = 0.022) and increased ANCA levels (adjusted HR 17.4, 95% CI 8.42-36.0, p < 0.001) were significantly associated with relapse. The median time from ANCA level increase to relapse was 0.6 months (IQR 0-2.1 mos). Conclusion. In our study, an increase in ANCA level during remission was associated with a risk of disease relapse. A rise in ANCA level may be useful for guiding treatment decisions in appropriate subsets of patients with ANCA-associated vasculitis.
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CLINICAL AND EXPERIMENTAL NEPHROLOGY 19(4) 718-724 2015年8月 査読有りPrevious studies have suggested that high neutrophil/lymphocyte ratios are related to worse outcome in patients with cardiovascular diseases. Patients with end-stage renal disease, especially those with inflammation, are at an increased risk of premature mortality, primarily because of cardiovascular disease. We aimed to clarify if high neutrophil/lymphocyte ratio is associated with increasing cardiovascular events in Japanese patients with end-stage renal disease. We enrolled 86 incident Japanese dialysis patients (58 men, age 58 +/- A 11 years) in a prospective cohort study. The median follow-up was for 38.7 months. The association between neutrophil/lymphocyte ratio at the start of dialysis therapy and clinical biomarkers was investigated. Relative risks and cumulative cardiovascular disease events were calculated. The median neutrophil/lymphocyte ratio reported was 3.72. The duration from the start of the dialysis therapy to the first cardiovascular disease event was significantly shorter as a neutrophil/lymphocyte ratio increased (log-rank test, P = 0.003). The relative risk of cardiovascular disease events in patients with neutrophil/lymphocyte ratio > median to cardiovascular events in patients with the ratio < median as a reference was 3.02 (95 % CI 1.32-8.00) in a Cox proportional hazard model. The cumulative cardiovascular disease events during the observational period was higher in patients with neutrophil/lymphocyte ratio > median (23.0 events 100 person-years) than in patients with the ratio < median (6.8 events 100 person-years). A higher neutrophil/lymphocyte ratio is associated with increased risk of cardiovascular disease events and is a stronger predictor of future events.
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PLOS ONE 10(6) e0129159. 2015年6月Objective Presepsin is highlighted as a diagnostic and prognostic marker of sepsis. Little information is available regarding the accurate association between presepsin levels and the degree of kidney function. We analyzed presepsin levels in patients with a glomerular filtration rate (GFR) in the categories G1 to G5, evaluated via inulin renal clearance test, and receiving hemodialysis (HD). Methods Patients who were not receiving HD were included if they had undergone inulin renal clearance measurements for the accurate measurement of GFR (measured GFR), and patients who were receiving hemodialysis (HD) were included if they had anuria. Exclusion criteria were infection, cancer, liver disease, autoimmune disorders, or steroid or immunosuppressant use. GFR category was defined as follows; G1: GFR >= 90 ml/min/1.73m(2), G2: GFR = 60 to 90 ml/min/1.73m(2), G3: GFR = 30 to 60 ml/min/1.73m(2), G4: GFR = 15 to 30 ml/min/1.73m(2), G5: GFR <= 15 ml/min/1.73m(2). Results Seventy-one patients were included. The median (IQR) presepsin values of patients in each GFR category were as follows: G1 + G2: 69.8 (60.8-85.9) pg/ml; G3: 107.0 (68.7-150.0) pg/ml; G4: 171.0 (117.0-200.0) pg/ml; G5: 251.0 (213.0-297.5) pg/ml; and HD: 1160.0 (1070.0-1400.0) pg/ml. The log-transformed presepsin values, excluding patients receiving HD, inversely correlated with the measured GFR (Pearson's correlation coefficient = -0.687, P < 0.001). The multivariate analysis revealed that measured GFR and hemoglobin levels significantly correlated with elevated presepsin levels. Conclusion Presepsin levels were markedly high in patients receiving HD, similar to values seen in patients with severe sepsis or septic shock. In patients who were not receiving HD, presepsin levels increased as GFR decreased. Thus, the evaluation of presepsin levels in patients with chronic kidney disease requires further consideration, and a different cutoff value is needed for diagnosing sepsis in such patients.
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Arthritis Rheumatol. 67((8)) 2185-2195 2015年5月 査読有り
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ACTA CARDIOLOGICA 70(2) 217-223 2015年4月 査読有りBackground Tolvaptan selectively binds to the vasopressin V2 receptor and inhibits reabsorption of free water. Although its efficacy for heart failure has been proven, its efficacy for chronic kidney disease (CKD) patients has not been assessed in detail. Methods We examined 20 CKD patients (13 men and 7 women) who presented with volume overload and who were administered tolvaptan. We assessed urine volume (UV) and blood biochemistry before administration (d0), 1 day after administration (d1), and 7 to 14 days after administration (d7-14). Results The mean age was 74.0 +/- 13.1 years. Besides CKD, there were 9, 8, and 5 patients with heart failure, liver failure or liver cirrhosis, and severe oedema, respectively. UV significantly increased from 959.0 +/- 503.8 mL/day at d0 to 1605.4 +/- 964.0 mL/day at d7-14 (P < 0.01). Serum creatinine levels were not exacerbated (3.89 +/- 3.43 mg/dL at d0 and 3.66 +/- 3.02 mg/dL at d7-14). Serum albumin (ALB) levels and urinary protein creatinine ratio (uPCR) did not correlate with UV change. Estimated glomerular filtration rate (eGFR) correlated with UV change from d0 to d1 (r = 0.6619, P < 0.01). Serum sodium elevation correlated with increased UV (r = 0.4951, P < 0.05). Conclusion Tolvaptan is useful to reduce volume overload without exacerbation of the renal function; its effect does not depend on ALB or uPCR. The eGFR correlated with the efficacy of tolvaptan. If UV increases drastically after tolvaptan administration, serum Na levels should be carefully monitored.
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J Rheumatology in press 2015年
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JOURNAL OF IMMUNOLOGY 193(10) 5129-5139 2014年11月 査読有りDiffuse pulmonary hemorrhage (DPH) is an uncommon but critical complication of systemic lupus erythematosus. Peritoneal administration of 2,6,10,14-tetramethylpentadecane (pristane) can recapitulate a lupus-like syndrome in mice, which can develop into DPH within a few weeks, especially in C57BL/6 mice. Mac-1 (CD11b/CD18), a leukocyte adhesion molecule, is known to play a role in inflammation by regulating migration of leukocytes into injured tissue. In this study, we aimed to clarify the role of Mac-1 in pristane-induced DPH, using Mac-1(-/-) and wild-type (WT) mice on a C57BL/6 background. After pristane injection, Mac-1(-/-) mice showed reduced prevalence of DPH and attenuated peritonitis compared with WT mice. Analysis of the peritoneal lavage on days 5 and 10 after pristane treatment revealed increased numbers of eosinophils and alternatively activated macrophages, but decreased numbers of neutrophils and classically activated macrophages in Mac-1(-/-) mice compared with WT. Enhanced production of IL-4 and IL-13, both key mediators of macrophage polarization toward the mannose receptor(+) (MMR+) phenotype, was observed in the peritoneal cavity of Mac-1(-/-) mice. Depletion of neutrophils and eosinophils or adoptive transfer of classically activated macrophages resulted in the exacerbation of pristane-mediated DPH in both WT and Mac-1(-/-) mice. Moreover, peritoneal transfer of F4/80(high)MMR(+) alternatively activated macrophages successfully reduced the prevalence of DPH in WT mice. Collectively, Mac-1 promoted acute inflammatory responses in the peritoneal cavity and the lungs by downregulating granulocyte migration and subsequent phenotypic conversion of macrophages in a pristane-induced systemic lupus erythematosus model.
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PLOS ONE 9(10) e110376. 2014年10月 査読有りBackground: Idiopathic membranous nephropathy (IMN) is increasingly seen in older patients. However, differences in disease presentation and outcomes between older and younger IMN patients remain controversial. We compared patient characteristics between younger and older IMN patients. Methods: We recruited 171 Japanese patients with IMN, including 90 (52.6%) patients <65 years old, 40 (23.4%) patients 65-70 years, and 41 (24.0%) patients >= 71 years. Clinical characteristics and outcomes were compared between younger and older IMN patients. Results: During a median observation period of 37 months, 103 (60.2%) patients achieved complete proteinuria remission, which was not significantly associated with patient age (P = 0.831). However, 13 (7.6%) patients were hospitalized because of infection. Multivariate Cox proportional hazards models identified older age [adjusted hazard ratio (HR) = 3.11, 95% confidence interval (CI): 1.45-7.49, per 10 years; P = 0.003], prednisolone use (adjusted HR = 11.8, 95% CI: 1.59-242.5; P = 0.014), and cyclosporine used in combination with prednisolone (adjusted HR = 10.3, 95% CI: 1.59-204.4; P = 0.012) as significant predictors of infection. A <25% decrease in proteinuria at 1 month after immunosuppressive therapy initiation also predicted infection (adjusted HR = 6.72, 95% CI: 1.51-37.8; P = 0.012). Conclusions: Younger and older IMN patients had similar renal outcomes. However, older patients were more likely to develop infection when using immunosuppressants. Patients with a poor response in the first month following the initiation of immunosuppressive therapy should be carefully monitored for infection and may require a faster prednisolone taper.
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現代医学 62(1) 17-26 2014年6月
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PLOS ONE 9(6) 2014年6月 査読有りBackground: Multiple studies have shown cigarette smoking to be a risk factor for chronic kidney disease. However, it is unknown whether smoking similarly increases the risk for progression of membranous nephropathy. Methods: This study used the Nagoya Nephrotic Syndrome Cohort Study (N-NSCS), including 171 patients with idiopathic membranous nephropathy (IMN) from 10 nephrology centers in Japan. The dose-response relationships between cigarette smoking and the outcomes were assessed by using multivariate Cox proportional hazards models adjusted for clinically relevant factors. The primary outcome was a 30% decline in the estimated glomerular filtration rate (eGFR). The secondary outcome was first complete remission (CR) of proteinuria. Results: During the observation period (median, 37 months; interquartile range, 16-71 months), 37 (21.6%) patients developed a 30% decline in eGFR and 2 (1.2%) progressed to ESRD. CR occurred in 103 (60.2%) patients. Multivariate Cox proportional hazards models revealed current smoking (adjusted hazard ratio [HR], 7.81 [95% confidence interval (CI), 3.17-19.7]), female sex (adjusted HR, 3.58 [95% CI, 1.87-8.00]), older age (adjusted HR, 1.71 [95% CI, 1.13-2.62] per 10 years), the number of cigarettes smoked daily (adjusted HR, 1.61 [95% CI, 1.23-2.09] per 10 cigarettes daily), and cumulative smoking of >= 40 pack-years (adjusted HR, 5.56 [95% CI, 2.17-14.6]) to be associated with a 30% decline in eGFR. However, smoking was not associated with CR. Conclusion: Smoking is a significant and dose-dependent risk factor for IMN progression. All patients with IMN who smoke should be encouraged to quit.
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LUPUS 23(4) 342-352 2014年4月 査読有りObjective: A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. Methods: Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. Results: In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. Conclusion: Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.
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CYTOTHERAPY 16(3) 357-368 2014年3月 査読有りBackground aims. In patients receiving peritoneal dialysis, fungal or yeast peritonitis has a poor prognosis. In rat peritoneum with mechanical scraping, severe peritonitis can be induced by zymosan, a component of yeast (Zy/scraping peritonitis). Administration of rat adipose tissue-derived stromal cells (ASCs) potentially can improve several tissue injuries. The present study investigated whether rat ASCs could improve peritoneal inflammation in Zy/scraping peritonitis. Methods. Rat ASCs were injected intraperitoneally on a daily basis in rats with Zy/scraping peritonitis. Results. Peritoneal inflammation accompanied by accumulation of inflammatory cells and complement deposition was suppressed by day 5 after injection of rat ASCs. The peritoneal mesothelial layer in Zy/scraping peritonitis with rat ASC treatment was restored compared with the peritoneal mesothelial layer without rat ASC treatment. Injected rat ASCs co-existed with mesothelial cells in the sub-peritoneal layer. In vitro assays showed increased cellular proliferation of rat mesothelial cells combined with rat ASCs by co-culture assays, confirming that fluid factors from rat ASCs might play some role in facilitating the recovery of rat mesothelial cells. Hepatocyte growth factor was released from rat ASCs, and administration of recombinant hepatocyte growth factor increased rat mesothelial cell proliferation. Conclusions. Because the peritoneal mesothelium shows strong expression of membrane complement regulators such as Crry, CD55 and CD59, restoration of the mesothelial cell layer by rat ASCs might prevent deposition of complement activation products and ameliorate peritoneal injuries. This study suggests the therapeutic possibilities of intraperitoneal rat AS C injection to suppress peritoneal inflammation by restoring the mesothelial layer and decreasing complement activation in fungal or yeast peritonitis.
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NEPHROLOGY DIALYSIS TRANSPLANTATION 29(2) 228-231 2014年2月 査読有り招待有り
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JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 24(4) 587-603 2013年4月 査読有りMesenchymal stromal cells (MSCs) derived from adipose tissue have immunomodulatory effects, suggesting that they may have therapeutic potential for crescentic GN. Here, we systemically administered adipose-derived stromal cells (ASCs) in a rat model of anti-glomerular basement membrane (anti-GBM) disease and found that this treatment protected against renal injury and decreased proteinuria, crescent formation, and infiltration by glomerular leukocytes, including neutrophils, CD8(+) T cells, and CD68(+) macrophages. Interestingly, ASCs cultured under low-serum conditions (LASCs), but not bone marrow-derived MSCs (BM-MSCs), increased the number of innmunoregulatory CD163(+) macrophages in diseased glomeruli. Macrophages cocultured with ASCs, but not with BM-MSCs, adopted an immunoregulatory phenotype. Notably, LASCs polarized macrophages into CD163(+) immunoregulatory cells associated with IL-10 production more efficiently than ASCs cultured under high-serum conditions. Pharmaceutical ablation of PGE(2) production, blocking the EP4 receptor, or neutralizing IL-6 in the coculture medium all significantly reversed this LASC-induced conversion of macrophages. Furthermore, pretreating LASCs with aspirin or cyclooxygenase-2 inhibitors impaired the ability of LASCs to ameliorate nephritogenic IgG-mediated renal injury. Taken together, these results suggest that LASCs exert renoprotective effects in anti-GBM GN by promoting the phenotypic conversion of macrophages to immunoregulatory cells, suggesting that LASC transfer may represent a therapeutic strategy for crescentic GN. J Am Soc Nephrol 24: 587-603, 2013. doi: 10.1681/ASN.2012030264
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American Journal of Pathology 182(2) 410-419 2013年2月 査読有りInflammatory cell infiltration and fibrin deposition play important roles in the development of crescentic glomerulonephritis (GN). In particular, activation of coagulation is an indispensable factor in crescent formation. However, the mechanisms underlying the pathogenesis of crescent formation have not been completely elucidated. We identified the growth factor midkine (MK) as a novel key molecule in the progression of crescentic GN induced by anti-glomerular basement membrane antibody. Despite the lack of significant differences in autologous and heterologous reactions, MK-deficient (Mdk -/-) mice unexpectedly showed a greater number of necrotizing glomerular injuries than wild-type (Mdk+/+) mice. Likewise, more tubulointerstitial damage was observed in Mdk-/- mice, and this damage positively correlated with glomerular injury. Plasminogen activator inhibitor (PAI)-1 was strongly induced in the injured glomerulus of Mdk -/- mice, particularly in crescents and endothelial cells. This enhanced PAI-1 production was associated with an increase in inflammatory cell infiltration and matrix deposition in the glomerulus and the interstitium of Mdk-/- mice. In line with these in vivo data, primary cultured endothelial cells derived from Mdk-/- mice exhibited higher PAI-1 mRNA expression on fibrin challenge and less fibrinolysis than Mdk+/+ mice. In contrast, the expression of plasminogen activators was not affected. Our combined data suggest that MK leads to a blockade of PAI-1, which is closely associated with the suppression of crescentic GN. © 2013 American Society for Investigative Pathology.
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CELL TRANSPLANTATION 22(2) 287-297 2013年 査読有りCurrent studies suggest that mesenchymal stromal cells (MSCs) improve acute kidney injury (AKI) via paracrine/endocrine effects. We established human adipose tissue-derived stromal cells (hASCs) cultured in low (2%) serum (hLASCs), which have great potential of tissue regeneration. The present study was performed to investigate the therapeutic effects of hLASCs on AKI and to clarify the mechanisms involved. In low serum, hASCs proliferated well, while human bone marrow-derived stromal cells (hBMSCs) did not. hLASCs secreted higher levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) than did hASCs cultured in high (20%) serum (hHASCs) or hBMSCs cultured in high serum (hHBMSCs). AKI was induced in nude rats by folic acid, and hLASCs, hHASCs or control medium were administered into the renal subcapsules. hLASCs significantly attenuated acute renal damage, while hHASCs showed far less effect. Furthermore, interstitial fibrosis observed on day 14 was less pronounced in the hLASCs group. Cell tracking experiment showed no evidence of transdifferentiation. Intravenous injection of hLASCs or hHBMSCs or subcapsular injection of hHBMSCs did not ameliorate AKI. Concerning the mechanisms, our in vivo experiments showed that HGF knockdown by siRNA impaired the ability of hLASCs to protect the kidney from acute injury whereas VEGF knockdown did not. In conclusion, hLASCs, but not hHASCs or hHBMSCs, ameliorated AKI via paracrine effects, and HGF is one of the key mediators.
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CLINICAL AND EXPERIMENTAL NEPHROLOGY 16(6) 883-891 2012年12月 査読有りPozzi et al. reported the effectiveness of steroid pulse therapy (Pozzi's regimen) in IgA nephropathy (IgAN). The present study was performed to clarify the predictive factors for IgAN patients treated with Pozzi's regimen. One hundred nine IgAN patients treated by Pozzi's regimen were observed for up to 112.6 (median 39.7) months, and remission of proteinuria (PR) and disappearance of urinary abnormalities [complete remission (CR)] after Pozzi's regimen were analyzed. Predictive factors for the glomerular filtration rate (GFR) slopes for up to 5 years were analyzed among 81 patients who were observed for at least 2 years. The outcome of a 50 % increase in sCr was compared between the CR and non-CR groups within 2 years. Cumulative PR and CR rates increased rapidly until 2 years (54.5 and 46.8 % at 2 years), and then slowly but steadily up to 6 years (72.8 and 66.4 % at 6 years). Baseline characteristics of the CR and non-CR groups within 2 years were similar except for proteinuria. GFR slope was steeper in the non-CR group than in the CR group (-2.44 +/- A 5.12 vs. -0.32 +/- A 3.34 ml/min/1.73 m(2)/year). On multivariate analysis, sex and CR within 2 years were associated with GFR slope. Kaplan-Meier analysis demonstrated a better survival rate in CR group patients without a 50 % increase in sCr (p = 0.024). Among IgAN patients treated with Pozzi's regimen, CR within 2 years predicts a good prognosis.
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Blood 120(22) 4421-4431 2012年11月 査読有り
書籍等出版物
23講演・口頭発表等
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Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2020年7月8日BACKGROUND: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. METHODS: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. RESULTS: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. CONCLUSIONS: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.
共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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