Diabetic nephropathy (DN) is one of the most important causes of end-stage renal disease. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus, which possesses various pharmacological activities. AS-IV prevents podocyte apoptosis and ameliorates renal injury in DN; however, few studies have focused on its effects on ion channels. The transient receptor potential channel 6 (TRPC6) is an important Ca2+-permeable ion channel in podocytes, which is involved in high glucose (HG)-induced podocyte apoptosis. The aim of the present study was to investigate whether AS-IV prevented HG-induced podocyte apoptosis via TRPC6. Cultured podocytes were pre-treated with 10, 20 or 40 mu M AS-IV for 1 h prior to HG exposure for 24 h. Apoptosis, cell viability, expression of TRPC6, nuclear factor of activated T cells (NFAT2) and B-cell lymphoma 2-associated X protein (Bax), as well as the intracellular Ca2+ concentration were subsequently analyzed. The results indicated that HG induced podocyte apoptosis and upregulation of TRPC6, and increased intracellular Ca2+. Furthermore, enhanced NFAT2 and Bax expression was detected. Conversely, AS-IV protected HG-induced podocyte apoptosis, downregulated TRPC6 expression and suppressed intracellular Ca2+ in HG-stimulated podocytes. AS-IV also suppressed NFAT2 and Bax expression. These results suggest that AS-IV may prevent HG-induced podocyte apoptosis via downregulation of TRPC6, which is possibly mediated via the calcineurin/NFAT signaling pathway.
[1]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Nephrol, 164 Lanxi Rd, Shanghai 200062, Peoples R China.
[2]Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Nephrol & Rheumatol, Shanghai 200233, Peoples R China.
[3]Fudan Univ, Sch Pharm, Dept Pharmacol, 826 Zhangheng Rd, Shanghai 201203, Peoples R China.
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