The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling  

作　　者：Siting Wei Meng Li Wanlu Song Jiaye Liu Shicheng Yu Yalong Wang Mengxian Zhang Huijun Du Yuan Liu Huidong Liu Wei Fu Baojie Li Ye-Guang Chen 

机构地区：[1]The State Key Laboratory of Membrane Biology,Tsinghua‑Peking Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing 100084,China [2]Guangzhou National Laboratory,Guangzhou 510005,China [3]Department of Thyroid and Parathyroid Surgery,West China Hospital,Sichuan University,Chengdu,Sichuan,China [4]Department of General Surgery,Peking University Third Hospital,Beijing,China [5]Bio‑X Institutes,Key Laboratory for the Genetics of Developmental and Neuro‑Psychiatric Disorders,Ministry of Education,Shanghai Jiao Tong University,Shanghai 200240,China [6]School of Basic Medicine,Jiangxi Medical College,Nanchang University,Nanchang 330031,China

出　　处：《Cell Regeneration》2023年第1期107-118,共12页细胞再生（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(31988101);the Natural Science Foundation of Jiangxi Province(20224ACB209001).

摘　　要：Paracrine signals play pivotal roles in organ homeostasis.Mesenchymal stromal cells(MSCs)play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized.Here,we identified prostaglandin E2(PGE2)secreted by cyclooxygenase(COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier.We found that MSCs-induced organoid swelling through paracrine effect in vitro,a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis.To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo,we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype.Moreover,PGE2 defects increased the susceptibility of intestinal epithelium to colitis.Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance,providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.

关 键 词：COLITIS Intestinal mucosal barrier Mesenchymal stromal cells ORGANOIDS Prostaglandin E2 

分 类 号：R33[医药卫生—人体生理学]