| First Author | Pinto VI | Year | 2014 |
| Journal | FASEB J | Volume | 28 |
| Issue | 1 | Pages | 453-63 |
| PubMed ID | 24097310 | Mgi Jnum | J:206618 |
| Mgi Id | MGI:5551561 | Doi | 10.1096/fj.13-233759 |
| Citation | Pinto VI, et al. (2014) Filamin A protects cells against force-induced apoptosis by stabilizing talin- and vinculin-containing cell adhesions. FASEB J 28(1):453-63 |
| abstractText | In mechanically loaded tissues such as weight-bearing joints, myocardium, and periodontal ligament, pathophysiological forces can disrupt cell-matrix contacts, which can induce cell death, leading to tissue and organ dysfunction. Protection against force-induced cell death may be mediated by filamin A (FLNa), an actin-binding protein that regulates beta1 integrin-mediated cell adhesion. We examined the affect of filamin expression on collagen distribution and cell death in the periodontal ligament, a force-loaded tissue. Conditional deletion of FLNa in fibroblasts was associated with 2-fold increase of acellular areas in periodontal ligament and 7-fold higher proportions of apoptotic cells. In cultured fibroblasts with FLNa knockdown, we examined the affect of supraphysiological forces (1 pN/mum(2) cell area; applied through the beta1 integrin) on recruitment of talin and vinculin to focal adhesions and on apoptosis. Compared with the wild type, FLNa-knockdown cells exhibited 3-fold increases in floating cells after overnight force application and a 2-fold increase in cell detachment. Force induced time-dependent reductions (P<0.05) in the numbers of activated beta1 integrin-, talin-, and vinculin-stained adhesions in FLNa-knockdown compared with those in wild-type cells. We conclude that FLNa protects against apoptosis in force-loaded cells, and this protection is mediated by enhanced formation and maturation of matrix adhesions. |
