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

Abstract

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.

Key Role of MicroRNA in the Regulation of Granulocyte Macrophage Colony-stimulating Factor Expression in Murine Alveolar Epithelial Cells during Oxidative Stress

“…It is enriched in cardiac myocytes (40) and vascular smooth muscle cells (41). In each instance, miR133 appears to play an important role suppressing cell growth (42,43) and expression of extracellular matrix constituents (44). Cardiac hypertrophy and fibrosis are associated with cell-specific decreases in miR133 expression (40,45).…”

Age‐related changes in miR‐143‐3p:Igfbp5 interactions affect muscle regeneration

“…Myoblast proliferation was assessed by Ki67 staining and MTS assay (Zhang et al ., 2012). Briefly, cells were transfected as indicated and the proportion of Ki67‐+ cells was assessed 48 h later (Goljanek‐Whysall et al ., 2012a).…”

Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity

“…The culture medium of adipocytes was collected for RNA extraction. Adipocytes were starved of serum for 4 h and then stimulated with 200 nmol/l insulin for 12 h. Myogenesis of C2C12 myoblasts was induced as described previously [19]. Cells were incubated with 5 ng/ml TGF-β (Santa Cruz Biotechnology, Santa Cruz, CA, USA), or as indicated, 50 ng/ml TNF-α (gift from Yingying Le, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China) and 1 μmol/l rosiglitazone (Cayman Chemical, Ann Arbor, MI, USA) for 12 h. Small interfering RNA (siRNA) oligos and miR-130b mimics were purchased from GenePharma (Shanghai, China).…”