Vitamin D receptor activation protects against lipopolysaccharide-induced acute kidney injury through suppression of tubular cell apoptosis.
Vitamin D receptor activation protects against lipopolysaccharide-induced acute kidney injury through suppression of tubular cell apoptosis.
Am J Physiol Renal Physiol. 2019 Mar 13;:
Authors: Du J, Jiang S, Hu Z, Tang S, Sun Y, He J, Li Z, Yi B, Wang J, Zhang H, Li YC
Abstract
Acute kidney injury (AKI) is a common complication of sepsis characterized by a rapid degradation of renal function. The effect of vitamin D on AKI remains poorly understood. Here we showed that vitamin D receptor (VDR) activation protects against lipopolysaccharide (LPS)-induced AKI by blocking renal tubular epithelial cell apoptosis. Mice lacking VDR developed more severe AKI than wild-type (WT) controls following LPS treatment, manifested by marked increases in body weight loss, accumulation of serum BUN and creatinine as well as the magnitude of apoptosis of tubular epithelial cells. In the renal cortex, LPS treatment led to more dramatic downregulation of Bcl2, more robust induction of PUMA and miR-155, and more severe caspase 3 activation in VDR knockout mice compared with WT controls. Conversely, paricalcitol pre-treatment markedly prevented LPS-induced AKI. Paricalcitol ameliorated body weight loss, attenuated serum BUN and creatinine accumulation, blocked tubular cell apoptosis, prevented the suppression of Bcl2 and reversed PUMA and miR-155 induction and caspase 3 activation in LPS-treated WT mice. In HK2 cells LPS induced PUMA and miR-155 by activati...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Du J, Jiang S, Hu Z, Tang S, Sun Y, He J, Li Z, Yi B, Wang J, Zhang H, Li YC Tags: Am J Physiol Renal Physiol Source Type: research