Vitamin D-VDR (vitamin D receptor) regulates defective autophagy in renal tubular epithelial cell in streptozotocin-induced diabetic mice via the AMPK pathway

• DOI: 10.1080/15548627.2021.1962681
• Publication Date: 2021-08-25T18:26:11Z
• Authors: Aimei Li; Bin Yi; Hailong Han; Shikun Yang; Zhaoxin Hu; Li Zheng; Jianwen Wang; Qin Liao; Hao Zhang
• Keywords: Paricalcitol

Diabetic nephropathy (DN) has become a major cause of end-stage renal disease, and autophagy disorder is implicated in the pathogenesis DN. Our previous studies found that vitamin D (VD) VDR (vitamin receptor) played renoprotective role by inhibiting inflammation fibrosis. However, whether VD-VDR regulates disorders DN remains unclear. In this study, we established streptozotocin (STZ)-induced diabetic model vdr knockout (vdr-KO) mice specifically overexpressed proximal tubular epithelial cells (Vdr-OE) mice. results showed paricalcitol (an activated analog) or Vdr-OE could alleviate STZ-induced ALB (albumin) excretion, tubule injury inflammation, while these were worsened vdr-KO Defective was observed kidneys STZ mice, which more pronounced be partially restored Vdr-OE. high glucose-induced HK-2 cells, defective decreased PRKAA1/AMPK phosphorylation observed, VDR-dependent manner. AMPK inhibitor abolished paricalcitol-induced activation, activator cells. Furthermore, paricalcitol-mediated activation abrogated CAMKK2/CaMKKβ inhibition, but not STK11/LKB1 knockout. Meanwhile, rescued Ca2+ concentration induced glucose. conclusion, can restore kidney attributed to Ca2+-CAMKK2-AMPK pathway cells.Abbreviations: ACTB/β-actin: actin beta;AGE: advanced glycation end-products;AMPK: AMP-activated protein kinase;CAMKK2/CaMKKβ: calcium-calmodulin dependent kinase 2;CQ: chloroquine;DN: nephropathy;HG: levels glucose;KO: knockout;LG: low glucose;MAP1LC3/LC3: microtubule associated 1 light chain 3;NOD2: nucleotide binding oligomerization domain containing 2;OE: overexpression;PAS: periodic acid Schiff; Pari: paricalcitol;PTECs: cells;RT: room temperature;SQSTM1/p62: sequestosome 1;STK11/LKB1: serine/threonine 11;STZ: streptozotocin;TEM: transmission electron microscopy;VD: D;VDR: receptor;WT: wild-type