Smad3是转化生长因子-β（TGF-β）介导的上皮-间质转化、纤维化、肿瘤抑制和转移的关键因素。
Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis.
作者信息
Roberts Anita B, Tian Fang, Byfield Stacey DaCosta, Stuelten Christina, Ooshima Akira, Saika Shizuya, Flanders Kathleen C
机构信息
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA.
出版信息
Cytokine Growth Factor Rev. 2006 Feb-Apr;17(1-2):19-27. doi: 10.1016/j.cytogfr.2005.09.008. Epub 2005 Nov 11.
Smads2 and 3 transduce signals of TGF-beta from the cell surface to the nucleus. We used mice with a targeted deletion of Smad3 to study the specific contributions of this signaling pathway to pathogenic effects of TGF-beta. Focusing on models involving epithelial-to-mesenchymal transition (EMT), including injury to the lens and retina of the eye and to the kidney, we have found that loss of Smad3 blocks EMT and attenuates development of fibrotic sequelae. Smad3 also plays a critical role in both the tumor suppressor and pro-metastatic effects of TGF-beta in carcinogenesis. These observations suggest that development of small molecule inhibitors of Smad3 might have clinical application in treatment of fibrotic diseases as well as late stage cancers.
Smad2和Smad3将转化生长因子β（TGF-β）的信号从细胞表面传导至细胞核。我们利用Smad3基因靶向缺失的小鼠来研究该信号通路对TGF-β致病作用的具体贡献。聚焦于涉及上皮-间充质转化（EMT）的模型，包括眼部晶状体和视网膜以及肾脏的损伤，我们发现Smad3的缺失会阻断EMT并减轻纤维化后遗症的发展。Smad3在TGF-β在致癌过程中的肿瘤抑制和促转移作用中也起着关键作用。这些观察结果表明，开发Smad3小分子抑制剂可能在纤维化疾病以及晚期癌症的治疗中具有临床应用价值。
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