Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development

Yuka Takehara-Kasamatsu, Kunihiro Tsuchida, Masashi Nakatani, Tatsuya Murakami, Akira Kurisaki, Osamu Hashimoto, Hideyo Ohuchi, Hitomi Kurose, Kazuhiro Mori, Shoji Kagami, Sumihare Noji, Hiromu Sugino

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)276-288
Number of pages13
JournalJournal of Medical Investigation
Volume54
Issue number3-4
DOIs
Publication statusPublished - 27-11-2007

Fingerprint

Follistatin
Activins
Myostatin
Genes
Muscle
Pulmonary Valve
Messenger RNA
Skeletal Muscle
Follistatin-Related Proteins
Atrial Septum
Ventricular Septum
Tricuspid Valve
Surface Plasmon Resonance
Transforming Growth Factors
Biosensing Techniques
Aortic Valve
Mitral Valve
Surface plasmon resonance
Pulmonary Artery
In Situ Hybridization

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Takehara-Kasamatsu, Yuka ; Tsuchida, Kunihiro ; Nakatani, Masashi ; Murakami, Tatsuya ; Kurisaki, Akira ; Hashimoto, Osamu ; Ohuchi, Hideyo ; Kurose, Hitomi ; Mori, Kazuhiro ; Kagami, Shoji ; Noji, Sumihare ; Sugino, Hiromu. / Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development. In: Journal of Medical Investigation. 2007 ; Vol. 54, No. 3-4. pp. 276-288.
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abstract = "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.",
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Takehara-Kasamatsu, Y, Tsuchida, K, Nakatani, M, Murakami, T, Kurisaki, A, Hashimoto, O, Ohuchi, H, Kurose, H, Mori, K, Kagami, S, Noji, S & Sugino, H 2007, 'Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development', Journal of Medical Investigation, vol. 54, no. 3-4, pp. 276-288. https://doi.org/10.2152/jmi.54.276

Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development. / Takehara-Kasamatsu, Yuka; Tsuchida, Kunihiro; Nakatani, Masashi; Murakami, Tatsuya; Kurisaki, Akira; Hashimoto, Osamu; Ohuchi, Hideyo; Kurose, Hitomi; Mori, Kazuhiro; Kagami, Shoji; Noji, Sumihare; Sugino, Hiromu.

In: Journal of Medical Investigation, Vol. 54, No. 3-4, 27.11.2007, p. 276-288.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development

AU - Takehara-Kasamatsu, Yuka

AU - Tsuchida, Kunihiro

AU - Nakatani, Masashi

AU - Murakami, Tatsuya

AU - Kurisaki, Akira

AU - Hashimoto, Osamu

AU - Ohuchi, Hideyo

AU - Kurose, Hitomi

AU - Mori, Kazuhiro

AU - Kagami, Shoji

AU - Noji, Sumihare

AU - Sugino, Hiromu

PY - 2007/11/27

Y1 - 2007/11/27

N2 - 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.

AB - 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.

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