TY - JOUR
T1 - Focal adhesion kinase family is involved in matrix contraction by transdifferentiated Müller cells
AU - Tsukahara, Rintaro
AU - Umazume, Kazuhiko
AU - McDonald, Kevin
AU - Kaplan, Henry J.
AU - Tamiya, Shigeo
N1 - Funding Information:
Grant information: Grant DM090475 from the DoD (S Tamiya); Unrestricted Grant from Research to Prevent Blindness, New York, NY; KY Lions Eye Foundation; KY Research Challenge Trust Fund (HJ Kaplan); JSPS KAKENHI Grant Number 26861470 (K Umazume).
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85027501008&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2017.08.010
DO - 10.1016/j.exer.2017.08.010
M3 - Article
C2 - 28818394
AN - SCOPUS:85027501008
SN - 0014-4835
VL - 164
SP - 90
EP - 94
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -