Nephronectin expression is regulated by SMAD signaling in osteoblast-like MC3T3-E1 cells.
Nephronectin expression is regulated by SMAD signaling in osteoblast-like MC3T3-E1 cells.
复制标题
DOI：
10.1016/j.bbrc.2012.07.106
复制
发表时间：
2012-08
影响因子：
3.1
通讯作者：
Masayuki Tsukasaki;A. Yamada;K. Yoshimura;Agasa Miyazono;Matsuo Yamamoto;M. Takami;Y. Miyamoto;N. Morimura;R. Kamijo
中科院分区：
文献类型：
--
作者：
Masayuki Tsukasaki;A. Yamada;K. Yoshimura;Agasa Miyazono;Matsuo Yamamoto;M. Takami;Y. Miyamoto;N. Morimura;R. Kamijo
肾连蛋白（Npnt）是一种细胞外基质蛋白，已知是整合素α8β1的配体。我们以前证明，在成骨细胞中，TGF-β通过ERK 1/2和JNK抑制Npnt表达。在这项研究中，我们发现，通过特异性抑制剂{2-[3-（6-甲基吡啶-2-基）-1H-吡唑-4-基]-1，5-萘啶}抑制TGF-β I型受体（TGF-β R1，Alk 5），可强烈诱导成骨样MC 3 T3-E1细胞中Npnt的表达。Alk 5激酶诱导的Npnt表达增加以时间和剂量依赖性方式发生，而该表达也通过引入Smad 2的siRNA诱导，Smad 2是TGF-β信号传导的中心细胞内介质。这些结果表明，在成骨细胞中，Npnt的表达受到Alk 5-SMAD信号通路的调节。
Nephronectin (Npnt) is an extracellular matrix protein known to be a ligand for the integrin α8β1. We previously demonstrated that Npnt expression was suppressed by TGF-β through ERK1/2 and JNK in osteoblasts. In this study, we found that inhibition of a TGF-β type I receptor (TGF-β R1, Alk5) by a specific inhibitor {2-[3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine} strongly induced Npnt expression in osteoblast-like MC3T3-E1 cells. The Alk5 inhibitor-induced increase of Npnt expression occurred in both time- and dose-dependent manners, while that expression was also induced by introduction of an siRNA for Smad2, a central intracellular mediator of TGF-β signaling. These results suggest that the expression of Npnt is regulated by the Alk5-SMAD signaling pathway in osteoblasts.