| First Author | Gerassimov N | Year | 2022 |
| Journal | FASEB J | Volume | 36 |
| Issue | 7 | Pages | e22385 |
| PubMed ID | 35734962 | Mgi Jnum | J:329398 |
| Mgi Id | MGI:7344262 | Doi | 10.1096/fj.202200464 |
| Citation | Gerassimov N, et al. (2022) Examining the lineage autonomous role of beta3-integrin in muscle regeneration. FASEB J 36(7):e22385 |
| abstractText | Skeletal muscles can regenerate over the lifetime from resident muscle stem cells (MuSCs). Interactions between MuSCs and extracellular matrix (ECM) proteins are essential for muscle regeneration. The best-known receptors for ECM proteins are integrins, a family composed of twenty-some heterodimeric combinations of an alpha- and a beta-subunit. beta1-integrin (encoded by Itgb1) is required for quiescence, proliferation, migration, and fusion of Pax7(+) MuSCs in the mouse model. beta3-integrin (encoded by Itgb3) has been reported to be critical for the myogenic differentiation of C2C12 myoblasts, and Itgb3 germline mutant mice were shown to regenerate few if any myofibers after injury. To investigate the autonomous role of Itgb3 in the myogenic lineage in vivo, we conditionally inactivated a floxed Itgb3 allele (Itgb3(F) ) by constitutive Pax7-Cre and tamoxifen-inducible Pax7-CreERT2 drivers. Unexpectedly, we found no defects in muscle regeneration in both conditional knockout models. In vitro studies using Itgb3 mutant myoblasts or RNAi knockdown of Itgb3 in myoblasts also did not reveal a role for myogenic differentiation. As beta1- and beta3-integrins share ECM ligands and downstream signaling effectors, we further examined Itgb3's role in a Itgb1 haploid background. Still, we found no evidence for an autonomous role of Itgb3 in muscle regeneration in vivo. Thus, while Itgb3 is critical for the differentiation of C2C12 cells, the regenerative defects reported for the Itgb3 germline mutant are not due to its role in the MuSC. We conclude that if beta3-integrin does have a role in Pax7(+) MuSCs, it is compensated by beta1- and/or another beta-integrin(s). |
