Decreased expression of H19/miR-675 ameliorates muscle atrophy by regulating the IGF1R/Akt/FoxO signaling pathway

Molecular Medicine

Research Article

Wenjiong Li¹  Fei Wang¹  Xiaoping Chen²  Shiming Li²  Xiangsheng Pang²  He Zhang³  Peng Zhang⁴  Yue Zhou⁵ 

[1] National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China;National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China;National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing, China;National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China;National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing, China;Department of Physical Education, Central South University, Changsha, Hunan, China;National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing, China;School of Sport Science, Beijing Sport University, Beijing, China;

关键词: LncRNA H19;    miR-675;    Muscle atrophy;    Hindlimb suspension;    Starvation;    IGF1R;   

DOI  :  10.1186/s10020-023-00683-w

 received in 2023-01-19, accepted in 2023-06-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLong non-coding RNA (lncRNA) H19 is one of the most highly expressed and conserved transcripts in mammalian development, and its functions have been fully discussed in many contexts including tumorigenesis and skeletal muscle development. However, its exact role in muscle atrophy remains largely unknown. This study investigated the effect of lncRNA H19 on muscle atrophy and the potential underlying mechanism.MethodsHindlimb suspension (HS) of C57BL/6 mice and starvation of C2C12 cells with PBS were conducted to induce atrophy. Real-time PCR and Western blotting were used to measure the expression of RNAs and proteins. LncRNA H19 and its encoded miR-675 were overexpressed or inhibited in different models of muscle atrophy. Immunofluorescence was carried out to examine the cross-sectional area (CSA) and minimal Feret’s diameter (MFD) of myofibers and myotube diameter.ResultsThe expression levels of lncRNA H19 and miR-675 were significantly reduced in both the soleus and gastrocnemius muscles in response to HS. Overexpression of lncRNA H19 led to an increase in Atrogin-1 mRNA expression, and this effect was reversed by inhibiting miR-675. The overexpression of miR-675 aggravated both HS- and starving-induced muscle atrophy by inhibiting the IGF1R/Akt signaling pathway and promoting FoxO/Atrogin-1 expression. Conversely, miR-675 inhibition had the opposite effects.ConclusionThe lncRNA H19/miR-675 axis can induce muscle atrophy, and its downregulation in mice with HS-induced muscle atrophy may act as a protective mechanism against this condition.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

42004_2023_911_Article_IEq60.gif

Fig. 1

42004_2023_911_Article_IEq041.gif

42004_2023_911_Article_IEq15.gif

42004_2023_911_Article_IEq12.gif

Fig. 4