YAMATO Masayuki    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Type I collagen induces mesenchymal cell differentiation into myofibroblasts through YAP-induced TGF-β1 activation.
Journal	Formal name：Biochimie Abbreviation：Biochimie ISSN code：(1638-6183)0300-9084(Linking)
Domestic / Foregin	Foregin
Publisher	Elsevier
Volume, Issue, Page	150,pp.110-130
Author and coauthor	LIU Xiaoling†, LONG Xinyu, LIU Weiwei, ZHAO Yeli, HAYASHI Toshihiko, YAMATO Masayuki, MIZUNO Kazunori, FUJISAKI Hitomi, HATTORI Shunji, TASHIRO Shin-Ichi, OGURA Takaaki, ATSUZAWA Yuji, IKEJIMA Takashi*
Publication date	2018/07
Summary	In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive. This study adopted three states of collagen I existing in ECM remodeling: molecular collagen, fibrillar collagen and gelatin to see what are characteristics in the effects on two cell lines of mesenchymal origin, murine 3T3-L1 embryonic fibroblast and murine C2C12 myoblasts. The results showed that all three forms of collagen I were capable of inducing these two cells to differentiate into myofibroblasts characterized by increased expression of alpha-smooth muscle actin (α-SMA) mRNA. The expression of α-SMA is positively regulated by TGF-β1. Nuclear translocation of Yes-associated protein (YAP) is involved in this process. Focal adhesion kinase (FAK) is activated in the cells cultured on molecular collagen-coated plates, contributing to YAP activation. On the other hand, in the cells cultured on fibrillar collagen gel or gelatin-coated plates, oxidative stress but not FAK induce YAP activation. In conclusion, the three physicochemically distinct forms of col I induce the differentiation of mesenchymal cells into myofibroblasts through different pathways.
DOI	10.1016/j.biochi.2018.05.005
PMID	29777737