Myostatin regulates proliferation and extracellular matrix mRNA expression in NIH3T3 fibroblasts

Myostatin regulates proliferation and extracellular matrix mRNA expression in NIH3T3 fibroblasts
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DOI:
10.2220/biomedres.33.355
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发表时间:
2012-12-01
影响因子:
1.2
通讯作者:
Nishimura, Takanori
Nishimura, Takanori
中科院分区:
医学4区
文献类型:
--
作者:
Hosaka, Yoshinao Z.;Ishibashi, Mika;Nishimura, Takanori

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本研究的目的是阐明骨骼肌质量的负性调节剂肌抑素对NIH3T3成纤维细胞增殖和细胞外基质(ECM)合成的影响。增殖测定显示,肌肉生长抑制素在任何使用的剂量下都减弱了细胞生长。高剂量的肌肉生长抑制素强烈抑制细胞增殖。此外,发现肌生长抑制素受体,激活素受体2B型(ActRIIB)分布在细胞上,并且还阐明肌生长抑制素增加细胞周期蛋白依赖性激酶抑制剂p21(p21)的表达。这些结果表明,高剂量的肌生长抑制素通过与抑制成肌细胞增殖相同的机制抑制成肌细胞增殖。然后,我们通过实时PCR检测肌生长抑制素对ECM分子(核心蛋白聚糖、双糖链蛋白聚糖、I型胶原、III型胶原、IV型胶原和V型胶原)mRNA表达的影响。实时荧光定量PCR结果显示,肌生成抑制素可增加成纤维细胞中核心蛋白聚糖、双糖链蛋白聚糖和I、IV、V型胶原的mRNA表达。结果表明,肌肉生长抑制素调节ECM合成培养的成纤维细胞。
The aim of this study was to clarify the effects of myostatin, which is a negative regulator of skeletal muscle mass, on the proliferation of NIH3T3 fibroblasts and the synthesis of extracellular matrix (ECM) by them. A proliferation assay revealed that myostatin attenuated cell growth at any of the doses used. High doses of myostatin strongly inhibited cell proliferation. Moreover, myostatin receptor, activin receptor type-2B (ActRIIB), was found to be distributed on cells and it was also clarified that myostatin increased the expression of cyclin-dependent kinase inhibitor p21 (p21). These results suggested that a high dose of myostatin inhibits fibroblast proliferation by the same mechanism as that for inhibition of myoblast proliferation. We then examined the effects of myostatin on the mRNA expression of ECM molecules (decorin, biglycan, type I collagen, type III collagen, type IV collagen and type V collagen) by real-time PCR. Real-time PCR showed that myostatin increased the mRNA of decorin, biglycan and collagen (types I, IV and V) in fibroblasts. The results suggest that myostatin regulates ECM synthesis in cultured fibroblasts.