Activin A is a potent activator of renal interstitial fibroblasts.
Activin A is a potent activator of renal interstitial fibroblasts.
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DOI：
10.1097/01.asn.0000103225.68136.e6
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Shin Yamashita;A. Maeshima;I. Kojima;Y. Nojima
中科院分区：
文献类型：
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作者：
Shin Yamashita;A. Maeshima;I. Kojima;Y. Nojima
本研究旨在探讨激活素-卵泡抑素系统在肾脏纤维化过程中的作用。免疫反应性激活素A在单侧输尿管梗阻的肾小管细胞中表达上调，而在正常和对侧肾中不表达。激活素A在大鼠肾成纤维细胞系（NRK-49F细胞）和原代培养的肾间质成纤维细胞中促进细胞增殖，增强I型胶原mRNA的表达，诱导α -平滑肌肌动蛋白的产生。相反，激活素A不影响α -平滑肌肌动蛋白和I型胶原在肾上皮小管细胞株LLC-PK1和MDCK中的表达。活化素A拮抗剂Follistatin可显著抑制NRK-49F细胞的增殖。在NRK-49F细胞中，缺乏细胞内激酶结构域的截断型II型激活素受体过表达阻断激活素信号通路，抑制细胞增殖，降低I型胶原mRNA的表达水平。激活素A的表达可由tgf - β 1或激活素A本身诱导。卵泡抑素或过表达截断型II激活素受体可降低tgf - β 1对I型胶原表达的诱导作用。这些结果表明，在肾脏纤维化过程中，小管细胞产生的激活素A作为一种旁分泌因子激活肾间质成纤维细胞。
The present study was conducted to examine the involvement of the activin-follistatin system in the fibrotic process of the kidney. Immunoreactive activin A was upregulated in tubular cells in the kidneys with unilateral ureteral obstruction but not in normal and contralateral kidneys. Activin A promoted cell proliferation, enhanced the expression of type I collagen mRNA, and induced the production of alpha-smooth muscle actin in a rat kidney fibroblast cell line (NRK-49F cells) as well as in primary cultured renal interstitial fibroblasts. In contrast, activin A did not affect the expressions of alpha-smooth muscle actin and type I collagen in renal epithelial tubular cell lines LLC-PK1, and MDCK. Follistatin, an antagonist of activin A, significantly inhibited cell proliferation in NRK-49F cells. Blockade of activin signaling by overexpression of truncated type II activin receptor, which lacked the intracellular kinase domain, decreased cell proliferation and reduced the expression level of type I collagen mRNA in NRK-49F cells. The expression of activin A was induced by TGF-beta 1 or activin A itself. Induction of type I collagen expression by TGF-beta 1 was reduced by follistatin or by overexpression of truncated type II activin receptor. These results suggest that activin A produced by tubular cells acts as a paracrine factor that activates renal interstitial fibroblasts during the fibrotic processes of the kidney.