Inhibitor of FTO, Rhein, Restrains the Differentiation of Myoblasts and Delays Skeletal Muscle Regeneration
Author:
Li Rongyang12, Cao Yan2, Wu Wangjun2, Liu Honglin2, Xu Shiyong1
Affiliation:
1. College of Animal Science and Food Engineering, Jinling Institute of Technology, Nanjing 210095, China 2. Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
Abstract
N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits FTO, a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, FTO and ALKBH5 expression increased while m6A levels decreased. After muscle injury, FTO and ALKBH5 expression initially rose but later fell, while m6A levels initially dropped and then recovered. Inhibition of FTO by Rhein reduced MyHC and MyoG expression, indicating myoblast differentiation suppression. In a mouse model, Rhein decreased MyHC expression and muscle fiber cross-sectional area, delaying muscle regeneration. Rhein’s ability to increase RNA m6A modification delays skeletal muscle remodeling post-injury, suggesting a new medicinal application for this plant extract.
Funder
National Science and Technology Major Project Major Agricultural Plan of New Variety Innovation of Jiangsu Province Postgraduate Research and Practice Innovation Program of Jiangsu Province funded by the Jiangsu Provincial Department of Education National Natural Science Foundation of China
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