title: Suppressors of cytokine signaling inhibit tubular epithelial cell-myofibroblast transdifferentiation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  SOCS-1 and SOCS-3 can prevent tubulointerstitial fibrosis by inhibiting TEMT, which may be connected with the activation of STAT1 and STAT3.
authors: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors: Qingjuan
authors: Q
authors: Liu
authors: Shuxia
authors: S
authors: Liu
authors: Yonghong
authors: Y
authors: Shi
authors: Hang
authors: H
authors: Li
authors: Jun
authors: J
authors: Hao
authors: Lingling
authors: L
authors: Xing
authors: Yanping
authors: Y
authors: Cao
authors: Huijun
authors: H
authors: Duan
mesh_terms: D000199:Actins / Q000378:metabolism; D054338:Cell Transdifferentiation; D024042:Collagen Type I / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000166:cytology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009130:Muscle, Smooth / Q000166:cytology; D058628:Myofibroblasts / Q000166:cytology*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D053583:Interleukin-1beta; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053613:Janus Kinase 1