Work

Vitamin D receptor modulates autophagy via miR-20a-5p/ATG16L1 axis to alleviate lipopolysaccharide-induced acute kidney injury

Year: 2025

Type: article

Abstract: Sepsis-associated acute kidney injury (S-AKI) is a critical and life-threatening clinical syndrome characterized by intricate pathophysiological mechanisms and lack of effective therapeutic strategies. Our previous investigations in a diabetic nephropathy model indicated the potential protective effect of the Vitamin D Receptor (VDR) in regulating autophagy. Nevertheless, the precise association and involvement regarding VDR and autophagy in sepsis-associated AKI remains unknown. This research aims to investigate the protective role and underlying mechanisms of VDR in mitigating S-AKI. Through establishment of S-AKI models in VDR knockout mice and treatment with vitamin D receptor agonist paricalcitol, we reported that VDR deficiency exacerbated renal functional deterioration and histological alterations induced by lipopolysaccharide, whereas VDR activation markedly ameliorated these impairments. Mechanistic inquiries revealed that VDR could restore the expression of ATG16L1, a key regulator in autophagosome formation, by inhibition of miR-20a-5p, thereby fostering autophagosome maturation and facilitating autophagic flux impaired by LPS in renal tubular epithelial cells. Moreover, luciferase and ChIP experiments corroborated the direct transcriptional regulation role of VDR on miR-20a-5p. Collectively, this investigation illuminates a novel pathway through which VDR regulate autophagic dysfunction induced by lipopolysaccharide via the VDR-miR20a-5p-ATG16L1 axis, thereby introducing a promising therapeutic target against sS-AKI.

Source: Renal Failure

DOI: 10.1080/0886022x.2025.2577852