Open AccessElevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
Author(s) -
Huang Li,
Sun Tingyi,
Hu Liangjun,
Hu Shilong,
Sun Haimei,
Zhao Fuqian,
Wu Bo,
Yang Shu,
Ji Fengqing,
Zhou Deshan
Publication year - 2020
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13252
Subject(s) - mucus , colitis , mucin , biology , chromosomal translocation , colorectal cancer , glycosylation , barrier function , mucin 2 , cancer research , immunology , microbiology and biotechnology , cancer , gene expression , biochemistry , gene , ecology , genetics
The risk of colitis and colorectal cancer increases markedly throughout adult life, endangering the health and lives of elderly individuals. Previous studies have proposed that bacterial translocation and infection are the main risk factors for these diseases. Therefore, in the present study, we aimed to identify the underlying mechanism by focusing on the mucus barrier function and mucin‐type O ‐glycosylation. We evaluated alterations in the colon mucus layer in 2‐, 16‐, and 24‐month‐old mice and aged humans. Aged colons showed defective intestinal mucosal barrier and changed mucus properties. The miR ‐ 124 ‐ 3p expression level was significantly increased in the aged distal colonic mucosa, which was accompanied by an increase in pathogens and bacterial translocation. Meanwhile, T‐synthase, the rate‐limiting enzyme in O ‐glycosylation, displayed an age‐related decline in protein expression. Further experiments indicated that miR ‐ 124 ‐ 3p modulated O ‐glycosylation by directly targeting T‐synthase. Moreover, young mice overexpressing miR ‐ 124 ‐ 3p exhibited abnormal glycosylation, early‐onset, and more severe colitis. These data suggest that miR ‐ 124 ‐ 3p predisposes to senile colitis by reducing T‐synthase, and the miR ‐ 124 ‐ 3p /T‐synthase/ O ‐glycans axis plays an essential role in maintaining the physiochemical properties of colonic mucus and intestinal homeostasis.