Astragaloside IV prevents high glucose-induced podocyte apoptosis via downregulation of TRPC6

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 μM 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.