miR-10a-5p and miR-10b-5p Regulate Gastrointestinal Dysmotility in Aged Mice
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Authors
Baek, Gain
Issue Date
2023
Type
Thesis
Language
Keywords
Aging , Gut motility , miR-10a , miR-10b , miRNAs
Alternative Title
Abstract
We previously identified miR-10a-5p and miR-10b-5p (miR-10a/b-5p), as key regulators in gastrointestinal (GI) motility and diabetes. Healthy pacemaker cells, known as intestinal cells of Cajal (ICC), in the GI tract abundantly express miR-10a/b-5p, which in turn promote the growth and differentiation of these cells and therefore regulate GI motility. However, the role of miR-10a/b-5p in regulating GI dysmotility in aged mice has not been explored. In this study, we found miR-10a/b-5p were highly expressed in late embryonic and early postnatal stages but gradually decreased in aged mice. Similarly, ICC in the colon progressively deteriorated in the old age group compared to the young age group. Body weight gradually increased with age. Fasting blood glucose levels remained normal in the young, middle, and old age groups. However, GI motility showed an age-dependent impairment as total GI transit time (TGITT) was significantly delayed in the old age group. In addition, colon transit time (CTT) was also significantly delayed in the middle age group and further delayed in the old age group, which showed similar patterns in fecal pellet output (FPO). To confirm whether GI motility was regulated via miR-10a/b-5p, we generated mir-10a and/or mir-10b knockout (KO) mice. GI motility (TGITT, CTT, and FPO) was impaired in mir-10a KO mice and mir-10b KO mice. We finally demonstrated delayed GI motility was improved in the old age mice by injection of a miR-10a-5p mimic, confirming the key role of miR-10a-5p in the restoration of GI motility. This study suggests that GI motility is regulated by miR-10a/b-5p-mediated ICC phenotype in aged mice.