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埼玉医科大学雑誌 第30巻 第1号 (2003年1月) 37-49頁 ◇論文(図表を含む全文)は，PDFファイルとなっています． PDF (7.3 MB) 原 著 尿細管上皮細胞におけるConnective Tissue Growth Factor（CTGF）発現の検討 小林 竜也 埼玉医科大学腎臓内科学教室〔平成14年12月10日 受付〕 Expression of Connective Tissue Growth Factor in Renal Tubular Epithelial Cells Tatsuya Kobayashi (Department of Nephrology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan) Background/Purpose: Connective tissue growth factor (CTGF) is a member of CCN family which mediates profibrotic effects of transforming growth factor-β1 (TGF-β1), promoting fibroblast proliferation and extracellular matrix (ECM) production. CTGF has been presumed to involve in a variety of organ fibrogenesis. In the kidney at health and a disease, by using in situ hybridization glomerular parietal and visceral epithelial cells, mesangial cells, and interstitial fibroblasts were shown to express CTGF. Recently, tubular epithelial cells have been also revealed to express CTGF especially in diabetic nephropathy. Therefore, in this study, I evaluated CTGF protein expression in the tubular epithelium of renal biopsy specimens by immunohistochemistry, and the expression regulation and the role of CTGF in the cultured tubular epithelial cells (mPTEC). Methods: Using an anti-CTGF antibody, I performed catalyzed signal amplification immunohistochemistry on renal biopsy specimens from patients with minimal change nephrotic syndrome (MCNS), diffuse proliferative lupus nephritis (DPLN), IgA nephropathy (IgAN), and diabetic nephropathy (DN). Using mPTEC cultured in monolayer and co-culture with renal fibroblasts (TFB), whether a given humoral factor could induce CTGF mRNA expression and whether CTGF derived from mPTEC could stimulate TFB to produce type I collagen were tested. The expression of mRNA and type I collagen were determined by ribonuclease protection assay and indirect enzyme-linked immunosorbent assay, respectively. Results: Significant CTGF expression in the tubular epithelium was found in parallel to the interstitial fibrosis in DN samples. In addition, it was revealed that glucocorticoid (GC) therapy resulted in significant induction of tubular CTGF expression in MCNS and DPLN. Among profibrotic growth factors and proinflammatory cytokines employed, only TGF-β1 could induce CTGF mRNA expression in mPTEC in time- and dose-dependent fashion. D-glucose and dexamethasone could also induce CTGF expression in mPTEC. CTGF derived from mPTEC by TGF-β1 and d-glucose could subsequently induce type I collagen production in TFB. Conclusion: Renal tubular epithelial cells can express CTGF in vivo and in vitro, which is likely involved in renal fibrogenesis at least in DN and other diseases undergoing GC therapy. Keywords: connective tissue growth factor (CTGF), tubular epithelial cells, transforming growth factor-β(TGF-β), d-glucose, glucocorticoid (GC) J Saitama Med School 2003;30:37-49 (Received December 10, 2002)
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