SDF-1α reduces fibronectin expression in rat mesangial cells induced by TGF-ß1 and high glucose through PI3K/Akt pathway.

ABSTRACT

Stromal cell-derived factor-1 (SDF-1) is a chemokine and plays an important role in cell migration, whereas its role in diabetic nephropathy has not been illustrated distinctly. We hypothesized that SDF-1α may have an effect on extracellular matrix (ECM) accumulations in mesangial cells exposed to transforming growth factor-ß1 (TGF-ß1) or high glucose in vitro. The exogenous SDF-1α was added into rat mesangial cells incubated with TGF-ß1 or high glucose in the medium. The expression of fibronectin (FN) was quantitated by real-time RT-PCR, and the change of Akt and Smad3 measured by western blotting. SDF-1α, its receptor C-X-C chemokine receptor type 4 (CXCR4) and FN mRNA were expressed in rat mesangial cells. Both TGF-ß1 and high glucose raised the mRNA expressions of CXCR4 and FN in the cells. SDF-1α inhibited the elevated FN mRNA expression induced by TGF-ß1 and high glucose through CXCR4 and PI3K/Akt signaling pathway, as the effect of SDF-1α was reversed by CXCR4 antagonist AMD3100 and PI3K inhibitor LY294002. Correspondingly, TGF-ß1 induced Smad3 phosphorylation was suppressed when PI3K/Akt signaling pathway was activated by SDF-1α. Based on these findings, we conclude that SDF-1α ameliorates TGF-ß1/high glucose induced ECM accumulations in mesangial cells, which may mediate through PI3K/Akt pathway. This novel mechanism may bring a new insight to our understandings of diabetic nephropathy.