Ren Xiao-Jun, Guan Guang-ju, Liu Gang, Zhang Taoyan, Liu Gao-Hong
Department of Nephropathy, the Second Affiliated Hospital, Medical College of Shandong University, 247 Beiyuan Street, Jinan, China.
Nephrology (Carlton). 2009 Apr;14(3):311-20. doi: 10.1111/j.1440-1797.2008.01059.x. Epub 2009 Mar 10.
The effect of activin A on tubulointerstitial fibrosis in diabetic nephropathy (DN) using streptozotocin (STZ)-induced diabetic rats and high glucose-cultured HK-2 cells was investigated.
Male Wistar rats were randomized into a normal control group (NC) and diabetes mellitus group (DM). Diabetes was induced by i.p. injection of STZ. Six rats were respectively killed 4, 8, 12 and 16 weeks after model establishment in each group. The changes of kidney weight/bodyweight (KW/BW), urine albumin excretion rate (AER) and creatinine clearance rate (Ccr) were determined. The morphology of tubulointerstitium was observed by light microscopy. Further biochemical analysis was provided using immunohistochemistry and real-time polymerase chain reaction. The different parameters in high glucose-cultured HK-2 cells were monitored by western blotting or enzyme-linked immunosorbent assay (ELISA) and the intervention of rh-follistatin on them was investigated.
Compared with the NC group, there was marked enlargement in the levels of KW/BW, AER, Ccr and interstitial fibrosis index, and the production of P-Smad2/3 and fibronectin in the DM group from 8 to 16 weeks. Activin betaA, mainly located in tubular epithelial cells, was significantly higher in the DM group than that in the NC group throughout the study periods. Follistatin was abundant in the NC group, but was diminished gradually in the DM group. High glucose may facilitate the synthesis of activin betaA, transforming growth factor (TGF)-beta, P-Smad2/3 and fibronectin in HK-2 cells while rh-follistatin inhibited them except TGF-beta.
Activin A is involved in tubulointerstitial fibrosis in DN by inducing the production of fibronectin through Smad signal pathway.
利用链脲佐菌素（STZ）诱导的糖尿病大鼠和高糖培养的HK-2细胞，研究激活素A对糖尿病肾病（DN）肾小管间质纤维化的影响。
将雄性Wistar大鼠随机分为正常对照组（NC）和糖尿病组（DM）。通过腹腔注射STZ诱导糖尿病。每组在模型建立后4、8、12和16周分别处死6只大鼠。测定肾重/体重（KW/BW）、尿白蛋白排泄率（AER）和肌酐清除率（Ccr）的变化。通过光学显微镜观察肾小管间质的形态。使用免疫组织化学和实时聚合酶链反应进行进一步的生化分析。通过蛋白质印迹法或酶联免疫吸附测定（ELISA）监测高糖培养的HK-2细胞中的不同参数，并研究重组卵泡抑素对其的干预作用。
与NC组相比，DM组在8至16周时KW/BW、AER、Ccr水平和间质纤维化指数明显升高，且P-Smad2/3和纤连蛋白的产生增加。激活素βA主要位于肾小管上皮细胞，在整个研究期间DM组均显著高于NC组。卵泡抑素在NC组丰富，但在DM组逐渐减少。高糖可能促进HK-2细胞中激活素βA、转化生长因子（TGF）-β、P-Smad2/3和纤连蛋白的合成，而重组卵泡抑素除TGF-β外可抑制它们。
激活素A通过Smad信号通路诱导纤连蛋白的产生，参与DN的肾小管间质纤维化。
