埼玉医科大学雑誌 第32巻 第1号 (2005年1月) 13-21頁 ◇論文(図表を含む全文)は，PDFファイルとなっています．
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Existence and Function of Renin-Angiotensin System in Renal Interstitial Fibroblast
Tomohiro Kikuta (Department of Nephrology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan)
Tubulointerstitial fibrosis (TIF) is considered a valid marker of progression of diabetic and non-diabetic nephropathy, that correlates negatively with creatinine clearance (CCr), and functional outcome. Since a number of clinical trails have revealed that angiotensin converting enzyme inhibitors (ACEi) slowed the rate of decline of renal function in proteinuric patients, it is suggested that ACEi can directly and/or indirectly affect TIF. Therefore, to test this hypothesis, we performed a prospective study for 3 years focusing on the effects of ACEi on functional outcome of patients with IgA nephropathy (IgAN) in relation to the degree of TIF. In the control group treated with amlodipine, the degree of TIF was negatively correlated with the reduction rate of CCr (dCCr), which was consistent with previous observation. By contrast, in the group treated with ACEi, the dCCr index was attenuated compared with the controls, and there was no correlation between the degree of TIF and the dCCr index. The latter suggested that ACEi had independent effects on renal fibrogenesis. Subsequently, we performed in vitro experiments to test whether angiotensin II(Ang II) and aldosterone (ALD) had direct profibrotic effects on cultured human renal fibroblasts. Human renal fibroblasts expressed Ang II type 1 receptor (AT1R) in vivo and in vitro. Ang II stimulated fibroblast proliferation, and type I collagen production of human renal fibroblasts via AT1R, especially in fibroblasts derived from a fibrosing kidney; this effect was partially mediated by secreted TGF-β. ALD could also promote proliferation of fibrosis-derived fibroblasts. In conclusion, ACEi can efficaciously retard the progression of IgAN with and without TIF equally, which is supposed to be partially due to its direct effects on renal fibrogenesis.
Keywords: angiotensin converting enzyme inhibitor, IgA nephropathy, proteinuria, fibrosis, fibroblast
J Saitama Med School 2005;32:13-21
(Received December 3, 2004)