Calcitriol attenuates renal tubular epithelial cells apoptosis via inhibiting p38MAPK signaling in diabetic nephropathy
- 18 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Acta Diabetologica
- Vol. 57 (11), 1327-1335
- https://doi.org/10.1007/s00592-020-01554-0
Abstract
Aims To observe the effect of calcitriol on tubular epithelial cells apoptosis in diabetic nephropathy (DN) and to explore the possible mechanism of its renal protection. Methods In vivo, DN rats established by streptozocin (STZ) were treated with or without calcitriol by gavage. Rats were killed at 18 weeks after treatment. In vitro, HK-2 cells were cultured in high glucose with or without 1,25-dihydroxyvitamin D3. In some experiments, P38MAPK activator anisomycin was applied to incubate HK-2 cells. Cell apoptosis was detected by TUNEL or Annexin V-FITC/PI staining with flow cytometry. Immunohistochemical staining was used to observe the expression of VDR in kidney. Protein expression of cleaved caspase-3, Bax, Bcl-2, VDR, pp38MAPK and p38MAPK was assessed by western blotting. Result Calcitriol treatment ameliorated the severity of proteinuria and reduced renal tubular epithelial cells apoptosis in DN rats. In addition, calcitriol treatment significantly increased renal VDR expression and reduced the expression of p-p38MAPK in rats. In vitro, 1,25-dihydroxyvitamin D3 decreased the apoptotic rate of HK-2 cells induced by high glucose. In accord with the results from animal study, 1,25-dihydroxyvitamin D3 increased VDR expression, but decreased p-p38MAPK expression in HK-2 cells. Moreover, P38MAPK activator anisomycin blocked the anti-apoptotic effect of 1,25-dihydroxyvitamin D3 on HK-2 cells. Conclusions Calcitriol attenuates renal tubular cells apoptosis via VDR activation which inhibits p38MAPK signaling in DN rats.Keywords
Funding Information
- National Natural Science Foundation of China (81570612, 81870497)
- Jiangsu Agricultural Science and Technology Independent Innovation Fund (BL2014080)
- Zhejiang Province Public Welfare Technology Application Research Project (2019AY32018)
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