| First Author | Kurbet AS | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 12 | Pages | 3334-3347 |
| PubMed ID | 27653694 | Mgi Jnum | J:239115 |
| Mgi Id | MGI:5824959 | Doi | 10.1016/j.celrep.2016.08.062 |
| Citation | Kurbet AS, et al. (2016) Sterile Inflammation Enhances ECM Degradation in Integrin beta1 KO Embryonic Skin. Cell Rep 16(12):3334-47 |
| abstractText | Epidermal knockout of integrin beta1 results in complete disorganization of the basement membrane (BM), resulting in neonatal lethality. Here, we report that this disorganization is exacerbated by an early embryonic inflammatory response involving the recruitment of tissue-resident and monocyte-derived macrophages to the dermal-epidermal junction, associated with increased matrix metalloproteinase activity. Remarkably, the skin barrier in the integrin beta1 knockout animals is intact, suggesting that this inflammatory response is initiated in a sterile environment. We demonstrate that the molecular mechanism involves de novo expression of integrin alphavbeta6 in the basal epidermal cells, which activates a TGF-beta1 driven inflammatory cascade resulting in upregulation of dermal NF-kappaB in a Tenascin C-dependent manner. Importantly, treatment of beta1 KO embryos in utero with small molecule inhibitors of TGF-betaR1 and NF-kappaB results in marked rescue of the BM defects and amelioration of immune response, revealing an unconventional immuno-protective role for integrin beta1 during BM remodeling. |
