Department of Pathology, Hebei Medical University, Shijiazhuang, China.
Am J Nephrol. 2011;34(2):142-51. doi: 10.1159/000329325. Epub 2011 Jul 4.
BACKGROUND/AIMS: Tubular epithelial cell-myofibroblast transdifferentiation (TEMT) can be induced by diverse cytokines. The suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling. This study is aimed at examining the role of SOCS-1 and SOCS-3 in TEMT induced by cytokines.
The cell ultrastructure was observed using transmission electron microscopy. The protein and mRNA levels of cytokeratin 18 (CK18) and α-smooth muscle actin (α-SMA) were detected by immunocytochemistry, Western blot and real-time PCR. The levels of phosphorylated-signal transducer and activator of transcription (p-STAT) 1 and 3 were detected by Western blot. The protein and mRNA levels of SOCS-1 and SOCS-3 were detected by Western blot and real-time PCR. The levels of collagen type I and fibronectin (FN) were determined by ELISA.
Interleukin-1β (IL-1β) and oncostatin M (OSM) were able to downregulate CK18 expression and upregulate α-SMA, p-STAT1, p-STAT3, collagen type I and FN expression in cultured human renal proximal tubular epithelial cells (HKCs), whereas pretreatment with AG490 prevented these expression changes from occurring. All of the changes induced by IL-1β or OSM could be decreased by SOCS-1 and SOCS-3 overexpression, and were increased by SOCS-1 and SOCS-3 knockdown.
SOCS-1 and SOCS-3 can prevent tubulointerstitial fibrosis by inhibiting TEMT, which may be connected with the activation of STAT1 and STAT3.
背景/目的：细胞因子可诱导管状上皮细胞-肌成纤维细胞转分化（TEMT）。细胞因子信号转导抑制因子（SOCS）蛋白负调控细胞因子信号转导。本研究旨在探讨 SOCS-1 和 SOCS-3 在细胞因子诱导的 TEMT 中的作用。
透射电镜观察细胞超微结构。免疫细胞化学、Western blot 和实时 PCR 检测细胞角蛋白 18（CK18）和α-平滑肌肌动蛋白（α-SMA）的蛋白和 mRNA 水平。Western blot 检测磷酸化信号转导子和转录激活子（p-STAT）1 和 3 的水平。Western blot 和实时 PCR 检测 SOCS-1 和 SOCS-3 的蛋白和 mRNA 水平。ELISA 法检测 I 型胶原和纤维连接蛋白（FN）的水平。
白细胞介素 1β（IL-1β）和抑瘤素 M（OSM）可下调培养的人近端肾小管上皮细胞（HKC）中 CK18 的表达，上调 α-SMA、p-STAT1、p-STAT3、I 型胶原和 FN 的表达，而 AG490 预处理可阻止这些表达变化的发生。SOCS-1 和 SOCS-3 的过表达可降低由 IL-1β 或 OSM 诱导的所有变化，而 SOCS-1 和 SOCS-3 的敲低则增加了这些变化。
SOCS-1 和 SOCS-3 可通过抑制 TEMT 来预防肾小管间质纤维化，这可能与 STAT1 和 STAT3 的激活有关。
