Facilitation of mucosal healing by estrogen receptor b in ulcerative colitis through suppression of branched-chain amino acid transport and subsequent triggering of autophagy in colonic epithelial cells  

作　　者：Yilei Guo Yanrong Zhu Jing Zhang Yue He Mianjiang Zhao Haochang Lin Zhifeng Wei Yufeng Xia Yue Dai 

机构地区：[1]Department of Pharmacology of Chinese Materia Medica,China Pharmaceutical University,Nanjing 211198,China [2]Department of Pharmacognosy,China Pharmaceutical University,Nanjing 211198,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第1期168-187,共20页药学学报(英文版)

基　　金：supported by National Natural Science Foundation of China(Nos.82174049 and 82073861).

摘　　要：Colonic mucosal healing is the ultimate goal of ulcerative colitis(UC)treatment,but it remains difficult to realize.Given the higher incidence of UC in males and the beneficial effect of estrogen on UC,we conducted this study to examine the therapeutic potential of estrogen receptor b(ERb),the primary ER subtype in colon,on mucosal healing in UC.Our study is the first to report that ERb activation degree was positively correlated with mucosal healing in patients with UC.Furthermore,ERb activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsyinduced colonic injuries.Mechanistically,ERb activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport,leading to focal adhesion kinase(FAK)activation.Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration,ultimately facilitating mucosal healing.ERb/colitis mice exhibited impaired mucosal healing compared to wild-type littermates,highlighting the crucial effect of ERb.Importantly,combination with ERb-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid,a standard UC treatment agent,against mouse colitis.These findings attest to the crucial role of ERb activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.

关 键 词：Ulcerative colitis Mucosal healing Estrogen receptorβ Large neutral amino acid transporter l Branched-chain amino acids transport AUTOPHAGY Focal adhesion kinase Cell migration 

分 类 号：R73[医药卫生—肿瘤]