Vitamin D Ameliorates Podocyte Injury by Enhancing Autophagy Activity in Diabetic Kidney Disease

Abstract

Introduction: Restoration of podocyte autophagy is considered as a feasible strategy for the treatment of diabetic kidney disease (DKD). This study aimed at investigating the protective effect and potential mechanism of vitamin D on podocyte injury of DKD. Methods: Type 2 diabetic db/db mice received intraperitoneal injections of vitamin D analogue paricalcitol 400ng/kg per day for 16 weeks. Immortalized mouse podocytes were cultured in high glucose (HG) medium with active vitamin D3 calcitriol or autophagy inhibitor 3-methyladeine. Renal function and urine albumin creatinine ratio were assessed at week 24. HE, PAS staining and electron microscopy were used to evaluate renal histopathology and morphological changes. Immunohistochemistry, immunofluorescence and western blot were used to evaluate protein expression of nephrin and podocin in kidney tissue and podocytes. The expression of autophagy- related proteins (LC3, beclin-1, VPS34) and apoptosis-related proteins (cleaved caspase 3, Bax) was determined by western blotting. Podocyte apoptosis was further evaluated by using flow cytometer. Results: Albuminuria in a db/db mouse model was markedly attenuated after treatment with paricalcitol. This was accompanied by alleviation of mesangial matrix expansion and podocyte injury. Besides, the impaired autophagy in podocytes under diabetic conditions was also markedly enhanced after paricalcitol or calcitriol treatment, accompanied by restored decreased podocyte slit diaphragm proteins podocin and nephrin. Furthermore, the protective effect of calcitriol against HG induced podocyte apoptosis could be abated by autophagy inhibitor 3-methyladenine. Conclusion: Vitamin D ameliorates podocyte injury of DKD by enhancing podocyte autophagy activity, which may become a potential candidate autophagy activator for the therapeutic interventions for DKD.

Artemisinin alleviates obesity‐related glomerulopathy by downregulating CYP24A1 expression

“…Recent studies have shown that vitamin D can decrease podocyte loss and inhibit podocyte hypertrophy in rodent diabetes nephropathy, 10 thus identifying podocytes as a potentially important target for the renoprotective actions of vitamin D. In some disease states, the expression of CYP24A1 is markedly elevated in kidney diseases, such as in CKD patients with acute renal inflammation, 11 despite being rendered vitamin D-deficient. Similarly to the present study, the increased expression of CYP24A1 was also observed in mice fed an HFD.…”

Total 25-Hydroxyvitamin D Is an Independent Marker of Left Ventricular Ejection Fraction in Heart Failure with Reduced and Mildly Reduced Ejection Fraction

“…Moreover, 1,25(OH) 2 D deficient mice developed glomerular (podocyte) injury, albuminuria, and subsequent kidney dysfunction, which were reversible upon exposure to 1,25(OH) 2 D [34]. Zhang et al also highlighted the protective effects of paricalcitol, a vitamin D analogue, in type 2 diabetic (db/db) mice, which attenuated albuminuria, podocyte injury, and mesangial matrix expansion, by improving autophagic activity [35]. Our patients with HF showed significant positive correlations between total 25(OH)D and serum albumin levels.…”

Bioconversion of vitamin D3 into calcitriol by Actinomyces hyovaginalis isolate CCASU- A11-2

“…Vitamin D deficiency results in the respective body functions and results in various pathological consequences such as bone-softening diseases in children and in adults (Szulc et al 2023 ). Recent studies have shown a correlation between vitamin D 3 deficiency and the occurrence of respiratory infections, cardiovascular diseases, some immunological and lung disorders, and some types of cancer (Afzal et al 2021 ; Rojano-Ortega and Berral-de la Rosa 2022 ; Sîrbe et al 2022 ; Zhang et al 2023 ). The synthesis of calcitriol is compromised in patients with hepatic and/or renal problems.…”