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Downregulation of SPIN90 promotes fibroblast activation via periostin‐FAK‐ROCK signaling module
Author(s) -
You Eunae,
Huh YunHyun,
Lee Jieun,
Ko Panseon,
Jeong Jangho,
Keum Seula,
Kim Jaegu,
Kwon Ahreum,
Song Woo Keun,
Rhee Sangmyung
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27600
Subject(s) - periostin , microbiology and biotechnology , extracellular matrix , myofibroblast , downregulation and upregulation , fibroblast , gene knockdown , focal adhesion , small interfering rna , signal transduction , chemistry , cellular differentiation , biology , rna , fibrosis , gene , pathology , medicine , biochemistry , in vitro
Abstract Alterations in mechanical properties in the extracellular matrix are modulated by myofibroblasts and are required for progressive fibrotic diseases. Recently, we reported that fibroblasts depleted of SPIN90 showed enhanced differentiation into myofibroblasts via increased acetylation of microtubules in the soft matrix; the mechanisms of the underlying signaling network, however, remain unclear. In this study, we determine the effect of depletion of SPIN90 on FAK/ROCK signaling modules. Transcriptome analysis of Spin90 KO mouse embryonic fibroblasts (MEF) and fibroblasts activated by TGF‐β revealed that Postn is the most significantly upregulated gene. Knockdown of Postn by small interfering RNA suppressed cell adhesion and myofibroblastic differentiation and downregulated FAK activity in Spin90 KO MEF. Our results indicate that SPIN90 depletion activates FAK/ROCK signaling, induced by Postn expression, which is critical for myofibroblastic differentiation on soft matrices mimicking the mechanical environment of a normal tissue.