转化生长因子-β家族成员对抑制性Smad6和Smad7 mRNA的诱导作用。

Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members.

作者信息

Afrakhte M, Morén A, Jossan S, Itoh S, Sampath K, Westermark B, Heldin C H, Heldin N E, ten Dijke P

机构信息

Unit of Pathology, University Hospital, Uppsala, S-751 85, Sweden.

出版信息

Biochem Biophys Res Commun. 1998 Aug 19;249(2):505-11. doi: 10.1006/bbrc.1998.9170.

DOI:10.1006/bbrc.1998.9170

PMID:9712726

Abstract

Smad6 and Smad7 function as intracellular antagonists in transforming growth factor-beta (TGF-beta) signaling. Here we report the isolation of human Smad6, which is closely related to Smad7. Smad6 and Smad7 mRNAs were differentially expressed in lung cancer cell lines and were rapidly and directly induced by TGF-beta1, activin and bone morphogenetic protein-7. Cross-talk between TGF-beta and other signaling pathways was demonstrated by the finding that epidermal growth factor (EGF) induced the expression of inhibitory SMAD mRNA. Moreover, whereas the phorbol ester PMA alone had no effect, it potentiated the TGF-beta1-induced expression of Smad7 mRNA. Ectopic expression of anti-sense Smad7 RNA was found to increase the effect of TGF-beta1, supporting its role as a negative regulator in TGF-beta signaling. Thus, expression of inhibitory Smads is induced by multiple stimuli, including the various TGF-beta family members, whose action they antagonize.

摘要

Smad6和Smad7在转化生长因子-β（TGF-β）信号传导中作为细胞内拮抗剂发挥作用。在此，我们报告了与Smad7密切相关的人类Smad6的分离。Smad6和Smad7 mRNA在肺癌细胞系中差异表达，并被TGF-β1、激活素和骨形态发生蛋白-7快速直接诱导。通过表皮生长因子（EGF）诱导抑制性SMAD mRNA表达这一发现，证明了TGF-β与其他信号通路之间的相互作用。此外，虽然佛波酯PMA单独没有作用，但它增强了TGF-β1诱导的Smad7 mRNA表达。发现反义Smad7 RNA的异位表达增加了TGF-β1的作用，支持其作为TGF-β信号传导负调节因子的作用。因此，抑制性Smads的表达由多种刺激诱导，包括它们所拮抗的各种TGF-β家族成员。