ID 111524
Author
Takehara-Kasamatsu, Yuka The University of Tokushima
Tsuchida, Kunihiro The University of Tokushima|Fujita Health University
Nakatani, Masashi The University of Tokushima|Fujita Health University
Murakami, Tatsuya Fujita Health University
Kurisaki, Akira The University of Tokushima
Hashimoto, Osamu Kitasato University
Ohuchi, Hideyo The University of Tokushima
Kurose, Hitomi The University of Tokushima
Mori, Kazuhiro The University of Tokushima
Sugino, Hiromu The University of Tokushima
Keywords
FLRG
myostatin
activin
follistatin
heart
Content Type
Journal Article
Description
Follistatin-related gene (FLRG) encodes a secretory glycoprotein that has characteristic cysteine-rich follistatin domains. FLRG protein binds to and neutralizes several transforming growth factor-β (TGF-β) superfamily members, including myostatin (MSTN), which is a potent negative regulator of skeletal muscle mass. We have previously reported that FLRG was abundantly expressed in fetal and adult mouse heart. In this study, we analyzed the expression of FLRG mRNA during mouse heart development. FLRG mRNA was continuously expressed in the embryonic heart, whereas it was very low in skeletal muscles. By contrast, MSTN mRNA was highly expressed in embryonic skeletal muscles, whereas the expression of MSTN mRNA was rather low in the heart. In situ hybridization and immunohistochemical analysis revealed that FLRG expressed in smooth muscle of the aorta and pulmonary artery, valve leaflets of mitral and tricuspid valves, and cardiac muscles in the ventricle of mouse embryonic heart. However, MSTN was expressed in very limited areas, such as valve leaflets of pulmonary and aortic valves, the top of the ventricular and atrial septa. Interestingly, the expression of MSTN was complementary to that of FLRG, especially in the valvular apparatus. Biochemical analyses with surface plasmon resonance biosensor and reporter assays demonstrated that FLRG hardly dissociates from MSTN and activin once it bound to them, and efficiently inhibits these activities. Our results suggest that FLRG could function as a negative regulator of activin family members including MSTN during heart development.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
54
Issue
3-4
Start Page
276
End Page
288
Sort Key
276
Published Date
2007-08
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences
Bioscience and Bioindustry