Modulation of cutaneous extracellular collagen contraction by phosphorylation status of p130Cas.

Skin can respond to various types of internal and/or external mechanostimuli, such as excessive tension caused by body growth or decompression due to weight loss, which significantly affect skin morphology. Mechanosensors, including p130Cas, are reported to play a role in deformation and subsequent recovery of various tissues including skeletal muscles and blood vessels. However, the role of mechanotransduction via p130Cas in the regulation of skin size remains unclear. In this report, p130Cas activation was manipulated using a fibroblast-embedded collagen gel model or mouse skin contraction model. Inhibition or activation of Src family kinase-mediated phosphorylation of p130Cas significantly depressed and accelerated collagen gel contraction, respectively. The results also demonstrated age-dependent depression of cutaneous p130Cas activation in vivo. Inhibition of p130Cas signaling in our mouse model significantly suppressed recovery from cutaneous deformation. Taken together, our study highlighted the important role of p130Cas in cutaneous mechanotransduction for skin homeostasis.