Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix.

Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice.

The role of homeobox genes in retinal development and disease.

Homeobox genes are an evolutionarily conserved class of transcription factors that are critical for development of many organ systems, including the brain and eye. During retinogenesis, homeodomain-containing transcription factors, which are encoded by homeobox genes, play essential roles in the regionalization and patterning of the optic neuroepithelium, specification of retinal progenitors and differentiation of all seven of the retinal cell classes that derive from a common progenitor. Homeodomain transcription factors control retinal cell fate by regulating the expression of target genes required for retinal progenitor cell fate decisions and for terminal differentiation of specific retinal cell types.

Filamin A protects cells against force-induced apoptosis by stabilizing talin- and vinculin-containing cell adhesions.

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 β1 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.

Force-induced apoptosis mediated by the Rac/Pak/p38 signalling pathway is regulated by filamin A.

Cells in mechanically challenged environments cope with high-amplitude exogenous forces that can lead to cell death, but the mechanisms that mediate force-induced apoptosis and the identity of mechanoprotective cellular factors are not defined. We assessed apoptosis in NIH 3T3 and HEK (human embryonic kidney)-293 cells exposed to tensile forces applied through β1-integrins. Apoptosis was mediated by Rac-dependent activation of p38α.