Focal adhesion kinase family is involved in matrix contraction by transdifferentiated Müller cells. (November 2017)

• Record Type: Journal Article
• Authors: Tsukahara, Rintaro; Umazume, Kazuhiko; McDonald, Kevin; Kaplan, Henry J.; Tamiya, Shigeo
• Is Part Of: Experimental eye research. Volume 164(2017)
• Page Start: 90
• Page End: 94
• Publication Date: 2017-11
• Subjects: Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2017.08.010
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Transdifferentiated Müller cells that adopt a fibroblastic/myofibroblastic phenotype have been identified in epiretinal membranes (ERMs) in several ocular disorders, and have been implicated to play a role in the formation and/or the contraction of ERMs. We have previously demonstrated that dasatinib, a dual inhibitor of Src-family kinases and Abl kinase, can prevent matrix contraction by transdifferentiated Müller cells. In this study, we examined molecules involved in matrix contraction downstream of primary dasatinib targets. Tyrosine phosphorylation of focal adhesion kinase (FAK) family members FAK and PYK2 was significantly reduced by dasatinib, and select inhibitors for these kinases PF431396, which inhibits both FAK and PYK2, and PF573228, which only inhibits FAK and not PYK2, significantly reduced matrix contraction by transdifferentiated Müller cells. Dasatinib and PF431396 significantly reduced phosphorylation of Hic-5, a protein implicated to play a role in focal adhesions and cell signaling. Our data shows that FAK family members are involved in matrix contraction by transdifferentiated Müller cells, and also implicates that Hic-5 is situated downstream of the FAK family within the signaling pathway. Highlights: Dasatinib, which prevents Muller cell matrix contraction, inhibits FAK/PYK2. Other FAK/PYK2 inhibitors significantly inhibited Muller cell matrix contraction. Phosphorylation of focal adhesion protein Hic-5 is reduced by FAK/PYK2 inhibition.