Endosulfan promotes cell proliferation and extracellular matrix accumulation through TGF-β/Smad signaling pathway in HRMCs

Endosulfan is an organochlorine pesticide, which poses a potential danger to human health and safety. It is known that dysfunction of glomerular mesangial cells causes glomerular sclerosis, associated with chronic kidney diseases. In the present study, we investigated the effects of endosulfan on cell proliferation and extracellular matrix accumulation (ECM) in human renal mesangial cells (HRMCs). Cells were treated with endosulfan, endosulfan (10 mu M) plus specific inhibitor of TGF-beta signaling (LY2109761) or antioxidant (NAC). The results showed that endosulfan significantly promoted cell proliferation, accompanied with the decrease of p27 mRNA expression and the increase in the mRNA expression levels of p21 and inflammatory factors IL-6/IL-8. qRT-PCR results showed that matrix metalloproteinase-2 (MMP2) and tissue metalloproteinase-3 (TIMP3) were down-regulated whereas laminin was up-regulated when exposure to endosulfan. Western blot results showed that p-Smad2/3 was up-regulated, while Smad7 was down-regulated when exposure to endosulfan, which were reversed in the presence of LY2109761. Endosulfan significantly decreased the activity of SOD and increased the MDA level and CAT activity, which were reversed in the presence of NAC. These findings suggest that endosulfan can cause excessive proliferation and massive accumulation of ECM through TGF-beta/Smad signaling pathway, and also induced oxidative stress and inflammation in HRMCs.