Imbalance of autophagy and apoptosis in intestinal epithelium lacking the vitamin D receptor

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Rong LuJun Sun

Abstract

Apoptosis and autophagy are dynamic processes that determine the fate of cells. Vitamin D receptor (VDR) deficiency in the intestine leads to abnormal Paneth cells and impaired autophagy function. Here, we will elucidate the mechanisms of the intestinal epithelial VDR regulation of autophagy and apoptosis. We used in vivo VDRlox and VDR∆IEC mice and ex vivo organoids generated from small intestine and colon tissues. We found that VDR deficiency induced more apoptotic cells and significantly increased cell death in the small intestine and colon of VDR∆IEC mice. The proapoptotic protein B-cell lymphoma 2 (BCL-2) associated X protein (Bax) was enhanced, whereas autophagy related 16 like 1 (ATG16L1) and Beclin-1 were decreased in the intestines of VDRΔIEC mice. Apoptosis induced by Bax reduced autophagy by decreasing Beclin-1. Physical interactions between Beclin-1 and Bcl-2 were increased in the VDR-deficient epithelia from mice. The growth of VDR∆IEC organoids was significantly slower with fewer Paneth cells than that of VDR+/+ organoids. The expression levels of Beclin-1 and lysozyme were decreased in VDR∆IEC organoids. Bacterial endotoxin levels were high in the serum from VDR∆IEC mice and made mice susceptible to colitis. In t...Continue Reading

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Citations

May 21, 2020·American Journal of Physiology. Cell Physiology·Yunzhan ZhangJian-Ying Wang
Jan 6, 2021·International Journal of Molecular Sciences·Carolina BattistiniJun Sun
Mar 16, 2021·Frontiers in Immunology·Ahmad Alatshan, Szilvia Benkő
Jun 5, 2020·Cellular and Molecular Gastroenterology and Hepatology·Yong-Guo ZhangJun Sun
Apr 24, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Zhixia SongShizhong Zhang
May 15, 2021·Stem Cell Research & Therapy·Panida SittipoYun Kyung Lee
Jun 24, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Laurel McGillisNicola L Jones

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