Activation of vitamin D receptor attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cell

Publication date: Available online 12 August 2019Source: Life SciencesAuthor(s): Yan Liu, Liu Li, Bin Yi, Zhao-Xin Hu, Ai-Mei Li, Cheng Yang, Li Zheng, Hao ZhangAbstractAimsVitamin D and its receptor, vitamin D receptor (VDR), have renoprotection effect against diabetic nephropathy (DN). But the exact mechanism has not been fully elucidated. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP) epoxygenase-derived metabolites of arachidonic acid, protecting against diabetes and DN. Herein, we hypothesized that activation of VDR attenuated high glucose-induced cellular injury in renal tubular epithelial cells partially through up-regulating CYP2J5 expression.Main methodsStreptozotocin (STZ) was injected to induce diabetic in wild type and Vdr−/− mice. The effects of VDR knockout and an activator of VDR, paricalcitol, on the renal injury were detected. In vitro, a murine kidney proximal tubule epithelial cell line BU.MPT induced by high glucose were treated with or without paricalcitol (30 mM) for 12 h or 24 h.Key findingsThe expression of CYP2J5 was significantly decreased both in wild type and Vdr−/− diabetic mice induced by STZ. The STZ-induced kidney architecture damage and apoptosis rate in Vdr−/− mice were more severe. In vitro, high glucose treatment strongly reduced the CYP2J5 expression and the synthesis of 14,15-EET in BU.MPT cells. Supplement of 14,15-EET significantly reduced the lactate dehydrogenase (LDH) release induced by high glucose in B...
Source: Life Sciences - Category: Biology Source Type: research