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成肌过程中转化生长因子-β3的分泌与转录调控

Secretion and transcriptional regulation of transforming growth factor-beta 3 during myogenesis.

作者信息

Lafyatis R, Lechleider R, Roberts A B, Sporn M B

机构信息

Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.

出版信息

Mol Cell Biol. 1991 Jul;11(7):3795-803. doi: 10.1128/mcb.11.7.3795-3803.1991.

DOI:10.1128/mcb.11.7.3795-3803.1991
PMID:1710772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC361150/
Abstract

Transforming growth factor-beta 3 (TGF-beta 3) mRNA is differentially expressed in developing and mature mouse tissues, including high-level expression in developing and adult cardiac tissue. We show now that TGF-beta 3 mRNA is also expressed highly in skeletal muscle as well as in the mouse skeletal myoblast cell line C2C12. We also show that C2C12 cells secrete TGF-beta 3, and that this TGF-beta is able to inhibit C2C12 myoblast fusion after activation. In order to begin to understand how the TGF-beta 3 promoter is regulated in specific tissues during development, we therefore studied the regulation of TGF-beta 3 during myoblast fusion. After fusion of C2C12 cells into myotubes, TGF-beta 3 mRNA levels increased eightfold as a result of increased TGF-beta 3 transcription. TGF-beta 3 transcriptional regulation was studied in myoblasts and myotubes by transfection of chimeric TGF-beta 3/CAT promoter plasmids. Chloramphenicol acetyltransferase (CAT) activity was stimulated in myoblasts by several upstream regions between -301 and -47 of the TGF-beta 3 promoter and by the TGF-beta 3 5' untranslated region. CAT activity directed by the TGF-beta 3 promoter in myotubes was stimulated by a distinct upstream region located between -499 and -221. Therefore, the high level of TGF-beta 3 mRNA expression in muscle cells appears to be dependent on multiple regulatory events during different stages of myogenesis.

摘要

转化生长因子-β3（TGF-β3）mRNA在发育中和成熟的小鼠组织中差异表达，包括在发育中的和成年心脏组织中的高水平表达。我们现在表明，TGF-β3 mRNA在骨骼肌以及小鼠骨骼肌成肌细胞系C2C12中也有高表达。我们还表明，C2C12细胞分泌TGF-β3，并且这种TGF-β在激活后能够抑制C2C12成肌细胞融合。为了开始了解在发育过程中TGF-β3启动子在特定组织中是如何被调控的，我们因此研究了成肌细胞融合过程中TGF-β3的调控。C2C12细胞融合成肌管后，由于TGF-β3转录增加，TGF-β3 mRNA水平增加了八倍。通过转染嵌合的TGF-β3/CAT启动子质粒，在成肌细胞和肌管中研究了TGF-β3的转录调控。氯霉素乙酰转移酶（CAT）活性在成肌细胞中受到TGF-β3启动子-301至-47之间的几个上游区域以及TGF-β3 5'非翻译区的刺激。在肌管中由TGF-β3启动子指导的CAT活性受到位于-499至-221之间的一个不同上游区域的刺激。因此，肌肉细胞中TGF-β3 mRNA的高水平表达似乎依赖于肌生成不同阶段的多种调控事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/fc46d8840845/molcellb00031-0411-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/f2f51400b95e/molcellb00031-0409-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/ed1624c8bd12/molcellb00031-0409-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/9d054d2f39a7/molcellb00031-0410-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/fc46d8840845/molcellb00031-0411-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/f2f51400b95e/molcellb00031-0409-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/ed1624c8bd12/molcellb00031-0409-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/9d054d2f39a7/molcellb00031-0410-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/824b/361150/fc46d8840845/molcellb00031-0411-a.jpg

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