Journal
METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 98, Issue -, Pages 95-103Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2019.06.008
Keywords
LC3; Vitamin D receptor; Nuclear translocation
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Funding
- New Xiangya Talent Project of Third Xiangya Hospital of Central South University [20160309]
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Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Vitamin D receptor (VDR) belongs to the nuclear receptor superfamily and exerts a renoprotective effect through inhibiting fibrosis. Microtubule-associated protein 1 light chain 3 (LC3), a key regulator of autophagy, is abundant in the nucleus, although its primary function is in the cytoplasm. The role of nuclear LC3 and the mechanism by which LC3 shuttles between the cytoplasm and nucleoplasm has not been fully elucidated. We found that LC3 binds to VDR in an LC3-interacting region (LIR)-independent manner and promotes the nuclear translocation of VDR. Further study indicated that LC3 promotes the formation of the VDR:retinoid X receptor (RXR) heterodimer and inhibits fibrogenic genes expression in HK-2 cells induced by high glucose. Our result demonstrates that LC3 is a negative regulator of high glucose-induced fibrogenic genes expression through its ability to promote VDR signaling. (C) 2019 Elsevier Inc. All rights reserved.
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