Human peritoneal mesothelial cell transformation into myofibroblasts; in response to TGF-β1 in vitro
Human peritoneal mesothelial cell transformation into myofibroblasts; in response to TGF-β1 in vitro
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DOI：
10.3892/ijmm.2010.574
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发表时间：
2011-02-01
影响因子：
5.4
通讯作者：
Xu, Hui-Mian
中科院分区：
文献类型：
--
作者：
Lv, Zhi-Dong;Na, Di;Xu, Hui-Mian
腹膜转移是胃癌患者死亡的主要原因之一。癌细胞与腹膜间的相互作用可能在肿瘤腹膜播散中起关键作用。人腹膜间皮细胞是覆盖腹膜腔并形成浆膜的单层鳞状上皮细胞。间皮细胞在胃癌腹膜播散中的确切作用仍有待确定。TGF-β 1是一种细胞因子，已知其能够诱导细胞增殖和转化变化，其表达与胃癌的腹膜转移和TNM分期相关。腹膜下环境中高水平的TGF-β 1可能在正常间皮细胞向肌成纤维细胞的转变中起关键作用。在这里，我们证明了由TGF-β 1激活的间皮细胞经历上皮-间质转化（EMT），间皮细胞向肌成纤维细胞的转化依赖于Smad 2信号。间皮细胞的EMT以α-平滑肌肌动蛋白和波形蛋白表达上调为标志。细胞角蛋白和E-钙粘蛋白的表达随着时间的推移而下降，在转化的间皮细胞。通过siRNA沉默敲低Smad 2基因显著抑制了间皮细胞向肌成纤维细胞的转变。我们的结论是，当暴露于TGF-β 1间皮细胞进行EMT涉及Smad 2信号。此外，间皮细胞可能是腹膜纤维化中肌成纤维细胞的来源，并为胃癌的扩散提供了有利的环境。
Peritoneal dissemination is one of the leading causes of death in gastric cancer patients. The interaction between carcinoma cells and the peritoneal lining may play a key role in tumor peritoneal dissemination. Human peritoneal mesothelial cells are a monolayer of squamous epithelial cells covering the peritoneal cavity and forming serosal membranes. The precise role of mesothelial cells in the peritoneal dissemination of gastric cancer remains to be identified. Expression of TGF-beta 1, a cytokine known for its capacity to induce proliferative and transformative changes in cells, has been correlated with peritoneal metastasis and TNM stages of gastric cancer. High levels of TGF-beta 1 in the subperitoneal milieu may play a key role in the transition of normal mesothelial cells to myofibroblasts. Here, we demonstrate that mesothelial cells activated by TGF-beta 1 undergo epithelial-mesenchymal transition (EMT) and that the transition of mesothelial cells to myofibroblasts is dependent on Smad2 signaling. EMT of mesothelial cells was marked by up-regulation of alpha-smooth muscle actin and vimentin expression. Cytokeratin and E-cadherin expression decreased over time in transformed mesothelial cells. Knockdown of Smad2 gene by siRNA silencing significantly suppressed the transition of mesothelial cells to myofibroblasts. We conclude that when exposed to TGF-beta 1 mesothelial cells undergo EMT which involves Smad2 signaling. Furthermore, mesothelial cells may be the possible source of myofibroblasts in peritoneal fibrosis and provide a favorable environment for the dissemination of gastric cancer.