Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene

Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene
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DOI:
10.1016/j.bbrc.2005.12.159
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发表时间:
2006-03-03
影响因子:
3.1
通讯作者:
Ikegawa, S
Ikegawa, S
中科院分区:
生物学4区
文献类型:
--
作者:
Mori, M;Nakajima, M;Ikegawa, S

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软骨中间层蛋白(CILP)是软骨组织中丰富的细胞外基质蛋白。 CILP 与常见的肌肉骨骼疾病有关,包括骨关节炎和腰椎间盘疾病。然而,CILP 基因的调控很大程度上是未知的。我们发现 CILP mRNA 表达由 TGF-β 1 诱导,并依赖于 TGF-β 受体的信号传导。 CILP 的 TGF-β1 诱导是由 Smad3 介导的,Smad3 直接通过 CILP 启动子区域中的顺式元件发挥作用。除 Smad3 之外的途径也参与 CILP 的 TGF-β1 诱导。这些观察结果,加上 CILP 蛋白结合并抑制 TGF-β1 的发现,表明 CILP 和 TGF-β1 可能形成控制软骨细胞代谢的功能反馈环。 (c) 2006 Elsevier Inc. 保留所有权利。
Cartilage intermediate layer protein (CILP) is an extracellular matrix protein abundant in cartilaginous tissues. CILP is implicated in common musculoskeletal disorders, including osteoarthritis and lumbar disc disease. Regulation of the CILP gene is largely unknown, however. We have found that CILP mRNA expression is induced by TGF-beta 1 and dependent upon signaling via TGF-beta receptors. TGF-beta 1 induction of CILP is mediated by Smad3, which acts directly through cis-elements in the CILP promoter region. Pathways other than Smad3 also arc involved in TGF-beta 1 induction of CILP. These observations, together with the finding that CILP protein binds and inhibits TGF-beta 1, suggest that CILP and TGF-beta 1 may form a functional feedback loop that controls chondrocyte metabolism. (c) 2006 Elsevier Inc. All rights reserved.