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Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
by
Sun, Ting‐yi
, Yang, Shu
, Zhao, Fu‐qian
, Huang, Li
, Wu, Bo
, Sun, Hai‐mei
, Hu, Liang‐jun
, Ji, Feng‐qing
, Hu, Shi‐long
, Zhou, De‐shan
in
Age
/ Aging
/ Antigens
/ Bacteria
/ Cancer
/ Colitis
/ Colon
/ Colorectal cancer
/ Colorectal carcinoma
/ Disease
/ E coli
/ Gene expression
/ Geriatrics
/ Glycosylation
/ glycosyltransferase
/ Health aspects
/ Homeostasis
/ Immune system
/ Inflammatory bowel disease
/ Intestine
/ Microbiota
/ microRNA
/ MicroRNAs
/ Mucin
/ Mucosa
/ Mucus
/ Older people
/ Original
/ Original Paper
/ Pathogenesis
/ Polysaccharides
/ Population
/ Risk factors
/ Tumor necrosis factor-TNF
/ Tumors
2020
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Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
by
Sun, Ting‐yi
, Yang, Shu
, Zhao, Fu‐qian
, Huang, Li
, Wu, Bo
, Sun, Hai‐mei
, Hu, Liang‐jun
, Ji, Feng‐qing
, Hu, Shi‐long
, Zhou, De‐shan
in
Age
/ Aging
/ Antigens
/ Bacteria
/ Cancer
/ Colitis
/ Colon
/ Colorectal cancer
/ Colorectal carcinoma
/ Disease
/ E coli
/ Gene expression
/ Geriatrics
/ Glycosylation
/ glycosyltransferase
/ Health aspects
/ Homeostasis
/ Immune system
/ Inflammatory bowel disease
/ Intestine
/ Microbiota
/ microRNA
/ MicroRNAs
/ Mucin
/ Mucosa
/ Mucus
/ Older people
/ Original
/ Original Paper
/ Pathogenesis
/ Polysaccharides
/ Population
/ Risk factors
/ Tumor necrosis factor-TNF
/ Tumors
2020
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Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
by
Sun, Ting‐yi
, Yang, Shu
, Zhao, Fu‐qian
, Huang, Li
, Wu, Bo
, Sun, Hai‐mei
, Hu, Liang‐jun
, Ji, Feng‐qing
, Hu, Shi‐long
, Zhou, De‐shan
in
Age
/ Aging
/ Antigens
/ Bacteria
/ Cancer
/ Colitis
/ Colon
/ Colorectal cancer
/ Colorectal carcinoma
/ Disease
/ E coli
/ Gene expression
/ Geriatrics
/ Glycosylation
/ glycosyltransferase
/ Health aspects
/ Homeostasis
/ Immune system
/ Inflammatory bowel disease
/ Intestine
/ Microbiota
/ microRNA
/ MicroRNAs
/ Mucin
/ Mucosa
/ Mucus
/ Older people
/ Original
/ Original Paper
/ Pathogenesis
/ Polysaccharides
/ Population
/ Risk factors
/ Tumor necrosis factor-TNF
/ Tumors
2020
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Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
Journal Article
Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
2020
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Overview
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. Young colons show intact inner layer and mucin‐type O‐glycosylation, limiting microbiota access to the epithelium. Age‐related alteration in miR‐124‐3p/T‐synthase/O‐glycans axis and reduction in mucus thickness weakened the mucus barrier, leading to abnormal bacterial intrusion and increased susceptibility to senile colitis.
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