IGF2BP3-mediated enhanced stability of MYLK represses MSC adipogenesis and alleviates obesity and insulin resistance in HFD mice.

Autor: Huang X; Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People's Republic of China., He W; Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China., Fan S; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, People's Republic of China., Li H; Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People's Republic of China. yegw@mail.sysu.edu.cn., Ye G; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, People's Republic of China. lihui@sysush.com.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Jan 10; Vol. 81 (1), pp. 17. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1007/s00018-023-05076-0
Abstrakt: Mesenchymal stem cells (MSCs) hold immense potential as multipotent stem cells and serve as a primary source of adipocytes. The process of MSC adipogenesis plays a crucial role in maintaining systemic metabolic homeostasis and has garnered significant attention in tissue bioengineering. N6-methyladenosine (m6A), the most prevalent RNA modification, is known to regulate cell fate and disease. However, the precise involvement of m6A readers in MSC adipogenesis remains unclear. In this study, we investigated the impact of IGF2BP3, a prominent m6A reader, on MSC adipogenesis. Our findings revealed a decrease in IGF2BP3 expression during the natural adipogenic differentiation of MSCs. Furthermore, IGF2BP3 was found to repress MSC adipogenesis by augmenting the levels of MYLK, a calcium/calmodulin-dependent kinase. Mechanistically, IGF2BP3 interacted with MYLK mRNA in an m6A-dependent manner, extending its half-life and subsequently inhibiting the phosphorylation of the ERK1/2 pathway, thereby impeding the adipogenic differentiation of MSCs. Additionally, we successfully achieved the overexpression of IGF2BP3 through intraperitoneal injection of adeno-associated virus serotype Rec2, which specifically targeted adipose tissue. This intervention resulted in reduced body weight and improved insulin resistance in high-fat diet mice. Overall, our study provides novel insights into the role of IGF2BP3 in MSC adipogenesis, shedding light on adipocyte-related disorders and presenting potential targets for related biomedical applications.
(© 2024. The Author(s).)
Databáze: MEDLINE
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