| First Author | Rognoni E | Year | 2014 |
| Journal | Nat Med | Volume | 20 |
| Issue | 4 | Pages | 350-9 |
| PubMed ID | 24681597 | Mgi Jnum | J:210448 |
| Mgi Id | MGI:5571208 | Doi | 10.1038/nm.3490 |
| Citation | Rognoni E, et al. (2014) Kindlin-1 controls Wnt and TGF-beta availability to regulate cutaneous stem cell proliferation. Nat Med 20(4):350-9 |
| abstractText | Kindlin-1 is an integrin tail binding protein that controls integrin activation. Mutations in the FERMT-1 gene, which encodes for Kindlin-1, lead to Kindler syndrome in man, which is characterized by skin blistering, premature skin aging and skin cancer of unknown etiology. Here we show that loss of Kindlin-1 in mouse keratinocytes recapitulates Kindler syndrome and also produces enlarged and hyperactive stem cell compartments, which lead to hyperthickened epidermis, ectopic hair follicle development and increased skin tumor susceptibility. Mechanistically, Kindlin-1 controls keratinocyte adhesion through beta1-class integrins and proliferation and differentiation of cutaneous epithelial stem cells by promoting alpha(v)beta(6) integrin-mediated transforming growth factor-beta (TGF-beta) activation and inhibiting Wnt-beta-catenin signaling through integrin-independent regulation of Wnt ligand expression. Our findings assign Kindlin-1 the previously unknown and essential task of controlling cutaneous epithelial stem cell homeostasis by balancing TGF-beta-mediated growth-inhibitory signals and Wnt-beta-catenin-mediated growth-promoting signals. |
