Division of Nephropathology, University of Erlangen-Nürnberg, Erlangen, Germany.
Lab Invest. 2012 Jun;92(6):812-26. doi: 10.1038/labinvest.2012.63. Epub 2012 Apr 2.
Mesangial cell (MC) migration is essential during glomerular repair and kidney development. The aim of the study was to identify marker/player for glomerular progenitor/reserve cells migrating into the glomerulus after MC injury and during glomerulogenesis in the rat. Experimental mesangial proliferative nephritis was induced in Sprague Dawley rats by intravenous injection of OX-7 antibody. We investigated mRNA expression profiles in isolated glomeruli from on days 0, 1, 2, 3, and 5 after induction of anti-Thy1 nephritis using Affymetrix microarray technology. Using self-organizing maps, transgelin was identified as a new marker for repopulating glomerular cells. Expression of transgelin during anti-Thy1 nephritis was investigated by northern blot, real-time PCR, western blot, and immunohistochemistry. Migration and proliferation assays using isolated MCs after transgelin knockdown by siRNA were performed to investigate the potential role of transgelin during glomerular repopulation. Transgelin mRNA was not detected in healthy glomeruli. It was strongly upregulated during the repopulation process starting on day 1, continued to be increased until day 5 and disappeared on day 7. Transgelin was specifically expressed at the edge of the migratory front during glomerular repopulation as indicated by transgelin/OX-7 double staining. Transgelin expression was similar in migrating vs non-migrating MCs in vitro. Blocking of transgelin expression by siRNA treatment resulted in inhibition of MC migration and proliferation. Transgelin was also expressed in MCs during glomerulogenesis and in biopsies from patients with IgA nephritis. In conclusion, transgelin in the kidney is upregulated in repopulating MCs in vivo and supports their migratory and proliferative repair response after injury.
肾小球系膜细胞(MC)迁移在肾小球修复和肾脏发育过程中至关重要。本研究旨在鉴定在 MC 损伤后和大鼠肾小球发生期间迁移到肾小球中的肾小球祖细胞/储备细胞的标记物/参与者。通过静脉注射 OX-7 抗体,在 Sprague Dawley 大鼠中诱导实验性系膜增生性肾炎。我们使用 Affymetrix 微阵列技术,在诱导抗 Thy1 肾炎后的第 0、1、2、3 和 5 天,对分离的肾小球中的 mRNA 表达谱进行了研究。使用自组织映射,发现转凝胶蛋白是一种新的用于再填充肾小球细胞的标记物。通过 northern blot、实时 PCR、western blot 和免疫组织化学研究了抗 Thy1 肾炎期间转凝胶蛋白的表达。使用 siRNA 敲低转凝胶蛋白后分离的 MC 进行迁移和增殖测定,以研究转凝胶蛋白在肾小球再填充过程中的潜在作用。在健康的肾小球中未检测到转凝胶蛋白 mRNA。在起始于第 1 天的再填充过程中,它被强烈上调,持续增加到第 5 天,并在第 7 天消失。转凝胶蛋白在肾小球再填充过程中,在迁移前沿的边缘特异性表达,如转凝胶蛋白/OX-7 双重染色所示。转凝胶蛋白的表达在体外迁移和非迁移 MC 中相似。通过 siRNA 处理阻断转凝胶蛋白的表达导致 MC 迁移和增殖受到抑制。转凝胶蛋白在肾小球发生期间和 IgA 肾炎患者的活检中也在 MC 中表达。总之,体内再填充 MC 中肾脏的转凝胶蛋白上调,并支持它们在损伤后的迁移和增殖修复反应。