| First Author | Danussi C | Year | 2011 |
| Journal | J Cell Biol | Volume | 195 |
| Issue | 1 | Pages | 131-45 |
| PubMed ID | 21949412 | Mgi Jnum | J:177724 |
| Mgi Id | MGI:5295900 | Doi | 10.1083/jcb.201008013 |
| Citation | Danussi C, et al. (2011) EMILIN1-alpha4/alpha9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. J Cell Biol 195(1):131-45 |
| abstractText | EMILIN1 promotes alpha4beta1 integrin-dependent cell adhesion and migration and reduces pro-transforming growth factor-beta processing. A knockout mouse model was used to unravel EMILIN1 functions in skin where the protein was abundantly expressed in the dermal stroma and where EMILIN1-positive fibrils reached the basal keratinocyte layer. Loss of EMILIN1 caused dermal and epidermal hyperproliferation and accelerated wound closure. We identified the direct engagement of EMILIN1 to alpha4beta1 and alpha9beta1 integrins as the mechanism underlying the homeostatic role exerted by EMILIN1. The lack of EMILIN1-alpha4/alpha9 integrin interaction was accompanied by activation of PI3K/Akt and Erk1/2 pathways as a result of the reduction of PTEN. The down-regulation of PTEN empowered Erk1/2 phosphorylation that in turn inhibited Smad2 signaling by phosphorylation of residues Ser245/250/255. These results highlight the important regulatory role of an extracellular matrix component in skin proliferation. In addition, EMILIN1 is identified as a novel ligand for keratinocyte alpha9beta1 integrin, suggesting prospective roles for this receptor-ligand pair in skin homeostasis. |
