医療科学部

Hisahide Takahashi

  (髙橋 久英)

Profile Information

Affiliation
School of Health Sciences, Faculty of Medical Technology, Fujita Health University
Degree
(BLANK)(Fujita Health University)

J-GLOBAL ID
200901059120541717
researchmap Member ID
1000102672

Misc.

 67
  • 発達腎研究会, 10(1) 62-65, 2002  
  • H Okada, S Ban, S Nagao, H Takahashi, H Suzuki, EG Neilson
    KIDNEY INTERNATIONAL, 58(2) 587-597, Aug, 2000  
    Background. The appearance of interstitial fibrosis in polycystic kidneys is emblematic of progressive disease. Matrix forming this scar tissue is derived from local renal cells in response to cystogenesis. We investigated the phenotype of collagen-producing cells in the cystic kidneys of DBA/2-pcy mice to better characterize the spectrum of interstitial cells associated with renal fibrogenesis. Methods. The extent of interstitial fibrosis and the number of fibroblasts in cystic kidneys were first quantitated over time using computer-assisted image analysis. Subsequently, antisera to four cell protein markers were studied by coexpression immunohistochemistry during progression of fibrosis using confocal microscopy. The antisera included fibroblast-specific protein 1 (FSP1) for fibroblast phenotype, alpha-smooth muscle actin (alpha-SMA) for contractile phenotype, vimentin (VIM) for mes enchymal phenotype, and heat shock protein 47 (HSP47) for interstitial collagen-producing phenotype. Results. Interstitial fibrosis in cystic kidneys gradually increased throughout the 30-week observation period of our study. With progression of cystogenesis, most of the tubules in pcy mice either dilated or disappeared with time. FSP1(+) fibroblasts were distributed sparsely throughout the renal interstitium of young pcy and wild-type mice. Their number increased in the widening fibrotic septa by 18 weeks of age and persisted through 30 weeks of the study interval. Some epithelia among remnant tubules trapped within fibrotic septa around adjacent cysts also acquired the phenotype of FSP1(+), HSP47(+) collagen-producing fibroblasts, suggesting a possible role for epithelial-mesenchymal transformation (EMT) in this process. Most FSP1(+) fibroblasts were alpha-SMA(-), but HSP47(+), suggesting they were producing collagen proteins for the extracellular matrix. alpha-SMA(+), FSP1(-), HSP47(+) or HSP47(-) cells were also observed, and the latter tended to distribute independently in a linear pattern, reminiscent of vasculature adjacent to forming cysts. VIM+ expression was not observed in alpha-SMA(+) cells. Conclusions. Many nonoverlapping as well as fewer overlapping populations of FSP1(+) and alpha-SMA(+) cells shared in the collagen expression associated with progressive fibrogenesis in pcy mice undergoing cystogenesis. Some FSP1(+) fibroblasts are likely derived from tubular epithelium undergoing EMT, while alpha SMA(+), VIM- cells probably represent vascular smooth muscle cells or pericytes surviving vessel attenuation during the chaos of fibrogenesis. Importantly, not all interstitial cells producing collagens are alpha SMA(+).
  • S Nagao, T Yamaguchi, M Kasahara, M Kusaka, J Matsuda, N Ogiso, H Takahashi, JJ Grantham
    AMERICAN JOURNAL OF KIDNEY DISEASES, 35(2) 221-226, Feb, 2000  
    Epithelial proliferation, extracellular matrix remodeling, and interstitial inflammation are central elements in the pathogenesis of slowly progressive polycystic kidney disorders. Probucol, an antioxidant that lowers plasma cholesterol, has been shown to decrease smooth muscle cell proliferation and macrophage accumulation in blood vessels and to prevent restenosis after coronary angioplasty, We determined in 30-day-old male BDF1-pcy hybrid mice (derived from mating DBA/2FG-pcy and C57BL/6FG-pcy) the effect of probucol administered in the diet (1%) for 200 days on kidney weight relative to body weight (KW/BW), cyst expansion, renal interstitial fibrosis, and serum urea nitrogen (SUN) concentration. Animals were fed a moderately high-protein diet (HPD, 36%) to accentuate the development of renal cysts and to promote interstitial fibrosis. Probucol decreased serum cholesterol from 68 to 16 mg/dL but had no effect on food intake or body weight. Probucol decreased relative kidney size from 4.16% +/- 0.55% to 2.64% +/- 0.12% KW/BW (P < 0.01), SUN from 30.5 +/- 1.8 to 25.9 +/- 1.0 mg/dL (P < 0.05), cystic index from 2.45 +/- 0.11 to 1.36 +/- 0.10 (P < 0.01), and fibrosis index from 2.40 +/- 0.11 to 1.82 +/- 0.08 (P < 0.01). We conclude that probucol ameliorates the progressive deterioration in renal function and structure in pcy mice ingesting a relatively high level of dietary protein. (C) 2000 by the National Kidney Foundation, Inc.