文献类型：期刊文献

英文题名：Attenuation of p38-Mediated miR-1/133 Expression Facilitates Myoblast Proliferation during the Early Stage of Muscle Regeneration

作者：Zhang, Duo[1];Li, Xihua[2];Chen, Chuchu[3];Li, Yuyin[1];Zhao, Lei[2];Jing, Yanyan[1];Liu, Wei[1];Wang, Xiaoyun[1];Zhang, Ying[1];Xia, Hongfeng[1];Chang, Yaning[3];Gao, Xiang[4,5];Yan, Jun[4,5,6];Ying, Hao[1]

机构：[1]Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Grad Sch, Shanghai, Peoples R China;[2]Fudan Univ, Childrens Hosp, Dept Neuromuscular Dis, Shanghai 200433, Peoples R China;[3]E China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China;[4]Nanjing Univ, Model Anim Res Ctr, Nanjing, Jiangsu, Peoples R China;[5]Nanjing Univ, MOE Key Lab Model Anim Dis Study, Nanjing, Jiangsu, Peoples R China;[6]Wenzhou Med Coll, Sch Life Sci, Zhejiang Prov Key Lab Technol & Applicat Model Or, Wenzhou, Peoples R China

年份：2012

卷号：7

期号：7

外文期刊名：PLOS ONE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000306751300046)】；

基金：This work was supported by grants from the One Hundred Talents Program of the Chinese Academy of Sciences, the Ministry of Science and Technology of China (973 Program 2009CB919000, 2010CB912500, 2010CB945100), the National Natural Science Foundation (30970587, 31070679), the Science and Technology Commission of Shanghai Municipality (10ZR1435000), Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-R-09), the Fundamental Research Funds for the Central Universities (Jun Yan), and Shanghai Charity Foundation (The Special Fund for DMD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

摘要：Myoblast proliferation following myotrauma is regulated by multiple factors including growth factors, signal pathways, transcription factors, and miRNAs. However, the molecular mechanisms underlying the orchestration of these regulatory factors remain unclear. Here we show that p38 signaling is required for miR-1/133a clusters transcription and both p38 activity and miR-1/133 expression are attenuated during the early stage of muscle regeneration in various animal models. Additionally, we show that both miR-1 and miR-133 reduce Cyclin D1 expression and repress myoblast proliferation by inducing G1 phase arrest. Furthermore, we demonstrate that miR-133 inhibits mitotic progression by targeting Sp1, which mediates Cyclin D1 transcription, while miR-1 suppresses G1/S phase transition by targeting Cyclin D1. Finally, we reveal that proproliferative FGF2, which is elevated during muscle regeneration, attenuates p38 signaling and miR-1/133 expression. Taken together, our results suggest that downregulation of p38-mediated miR-1/133 expression by FGF2 and subsequent upregulation of Sp1/Cyclin D1 contribute to the increased myoblast proliferation during the early stage of muscle regeneration.