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DOI | 10.1038/s41467-019-10937-z |
LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival | |
Bayrer, James R.1,2; Wang, Hongtao3; Nattiv, Roy1; Suzawa, Miyuki2; Escusa, Hazel S.2; Fletterick, Robert J.4; Klein, Ophir D.5,6,7; Moore, David D.8; Ingraham, Holly A.2 | |
2019-06-26 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Epithelial dysfunction and crypt destruction are defining features of inflammatory bowel disease (IBD). However, current IBD therapies targeting epithelial dysfunction are lacking. The nuclear receptor LRH-1 (NR5A2) is expressed in intestinal epithelium and thought to contribute to epithelial renewal. Here we show that LRH-1 maintains intestinal epithelial health and protects against inflammatory damage. Knocking out LRH-1 in murine intestinal organoids reduces Notch signaling, increases crypt cell death, distorts the cellular composition of the epithelium, and weakens the epithelial barrier. Human LRH-1 (hLRH-1) rescues epithelial integrity and when overexpressed, mitigates inflammatory damage in murine and human intestinal organoids, including those derived from IBD patients. Finally, hLRH-1 greatly reduces disease severity in T-cell-mediated murine colitis. Together with the failure of a ligand-incompetent hLRH-1 mutant to protect against TNF alpha-damage, these findings provide compelling evidence that hLRH-1 mediates epithelial homeostasis and is an attractive target for intestinal disease. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000446846000001 |
WOS关键词 | LIVER RECEPTOR HOMOLOG-1 ; EXTRAADRENAL GLUCOCORTICOID SYNTHESIS ; BOWEL-DISEASE ; STRUCTURAL BASIS ; GENE-EXPRESSION ; BETA-CATENIN ; STEM-CELLS ; DIFFERENTIATION ; NR5A2 ; PROLIFERATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204431 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Calif San Francisco, Dept Pediat, Div Gastroenterol, Mission Bay Campus, San Francisco, CA 94158 USA; 2.Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Mission Bay Campus, San Francisco, CA 94158 USA; 3.Baylor Coll Med, Dept Pediat, Div Gastroenterol, Houston, TX 77030 USA; 4.Univ Calif San Francisco, Dept Biochem & Biophys, Mission Bay Campus, San Francisco, CA 94158 USA; 5.Univ Calif San Francisco, Dept Orofacial Sci, Mission Bay Campus, San Francisco, CA 94158 USA; 6.Univ Calif San Francisco, Program Craniofacial Biol, Mission Bay Campus, San Francisco, CA 94158 USA; 7.Univ Calif San Francisco, Dept Pediat, Div Genet, Mission Bay Campus, San Francisco, CA 94158 USA; 8.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA |
推荐引用方式 GB/T 7714 | Bayrer, James R.,Wang, Hongtao,Nattiv, Roy,et al. LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Bayrer, James R..,Wang, Hongtao.,Nattiv, Roy.,Suzawa, Miyuki.,Escusa, Hazel S..,...&Ingraham, Holly A..(2019).LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival.NATURE COMMUNICATIONS,9. |
MLA | Bayrer, James R.,et al."LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival".NATURE COMMUNICATIONS 9(2019). |
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