Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress

肥胖相关的脂质运载蛋白 2 上调通过减少内质网应激保护胃粘膜细胞免于凋亡

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作者:Xin Wen #, Bin Su #, Mingming Gao, Jiaqi Chen, Donglei Zhou, Hui You, Nannan Li, Shuaikang Chang, Xiaoyun Cheng, Chunhua Qian, Jingyang Gao, Peng Yang, Shen Qu, Le Bu

Abstract

Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.

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