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.
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Xing-Mei
XM
Yao
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Yu-Jun
YJ
Liu
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Yun-Man
YM
Wang
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Hao
H
Wang
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Bing-Bing
BB
Zhu
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Yong-Ping
YP
Liang
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Wei-Guo
WG
Yao
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Hui
H
Yu
Department of Nephrology and Rheumatology, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, P.R. China.
Nian-Song
NS
Wang
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
Xue-Mei
XM
Zhang
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Wen
W
Peng
D017209:Apoptosis / Q000187:drug effects*; D019703:Calcineurin / Q000378:metabolism; D002461:Cell Line, Transformed; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D050052:TRPC Cation Channels / Q000096:biosynthesis*; D000074287:TRPC6 Cation Channel; D014315:Triterpenes / Q000494:pharmacology*
D050778:NFATC Transcription Factors; D012503:Saponins; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; D014315:Triterpenes; C492146:Trpc6 protein, mouse; C052064:astragaloside A; D019703:Calcineurin; D005947:Glucose