Suppressors of cytokine signaling inhibit tubular epithelial cell-myofibroblast transdifferentiation.

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.

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.