| First Author | Longmate WM | Year | 2017 |
| Journal | J Cell Biol | Volume | 216 |
| Issue | 5 | Pages | 1473-1488 |
| PubMed ID | 28416479 | Mgi Jnum | J:249498 |
| Mgi Id | MGI:5921407 | Doi | 10.1083/jcb.201510042 |
| Citation | Longmate WM, et al. (2017) Suppression of integrin alpha3beta1 by alpha9beta1 in the epidermis controls the paracrine resolution of wound angiogenesis. J Cell Biol 216(5):1473-1488 |
| abstractText | Development of wound therapies is hindered by poor understanding of combinatorial integrin function in the epidermis. In this study, we generated mice with epidermis-specific deletion of alpha3beta1, alpha9beta1, or both integrins as well as keratinocyte lines expressing these integrin combinations. Consistent with proangiogenic roles for alpha3beta1, alpha3-null keratinocytes showed reduced paracrine stimulation of endothelial cell migration and survival, and wounds of epidermis-specific alpha3 knockout mice displayed impaired angiogenesis. Interestingly, alpha9beta1 in keratinocytes suppressed alpha3beta1-mediated stimulation of endothelial cells, and wounds of epidermis-specific alpha9 knockout mice displayed delayed vascular normalization and reduced endothelial apoptosis, indicating that alpha9beta1 cross-suppresses alpha3beta1 proangiogenic functions. Moreover, alpha9beta1 inhibited alpha3beta1 signaling downstream of focal adhesion kinase (FAK) autoactivation at the point of Src-mediated phosphorylation of FAK Y861/Y925. Finally, alpha9beta1 cross-suppressed many alpha3beta1-dependent genes, including the gene that encodes MMP-9, which we implicated as a regulator of integrin-dependent cross talk to endothelial cells. Our findings identify a novel physiological context for combinatorial integrin signaling, laying the foundation for therapeutic strategies that manipulate alpha9beta1 and/or alpha3beta1 during wound healing. |
