1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy

Abstract

Background/Aims: A recent study has shown that 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D, can ameliorate renal dysfunction. In this study, we aimed to determine the role of 1,25-D3 in angiotensin (Ang II)-induced renal injury and investigate the underlying mechanisms involved. Methods: C57BL/6J mice were treated with Ang II and/or 1,25-D3 (or saline as the control) for 2 weeks. Renal injury was evaluated using transmission electron microscopy and periodic acid-Schiff reagent and Masson’s trichrome staining. The pro-fibrotic and pro-inflammatory factors were assessed using real-time PCR. The renal apoptotic pathway was evaluated with TUNEL staining and western blot. Mitochondrial dysfunction (MtD) was determined using real-time PCR and electron microscopy. The activation of autophagy was detected using western blot. Results: In the Ang II-infused mice, expanded mesangial regions, tubulointerstitial fibrosis, and foot process fusion were observed; the levels of the pro-fibrotic and pro-inflammatory cytokines and MtD were also increased when compared with the control group. However, we found that administration of 1,25-D3 significantly improved renal function and MtD and reduced the pro-fibrotic and pro-inflammatory cytokine levels. Furthermore, 1,25-D3 significantly inhibited Ang II-induced autophagy dysfunction (determined by inhibition of Beclin-1 activation and reduction of the LC3-II/LC3-I ratio). Conclusion: Our findings suggest that 1,25-D3 may attenuate Ang II-induced renal injury by improving MtD and modulating autophagy. 1,25-D3 may be a new therapeutic for the treatment of CKD.