Localization of ανβ6 integrin-TGF-β1/Smad3, mTOR and PPARγ in experimental colorectal fibrosis.
Localization of ανβ6 integrin-TGF-β1/Smad3, mTOR and PPARγ in experimental colorectal fibrosis.
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DOI：
10.4081/ejh.2013.e40
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发表时间：
2013-12-04
期刊：
影响因子：
--
通讯作者：
Gaudio E
中科院分区：
文献类型：
--
作者：
Latella G;Vetuschi A;Sferra R;Speca S;Gaudio E
几种促纤维化介质的同时作用似乎与纤维化的发展有关。有证据表明，转化生长因子-β(转化生长因子-β)/Smad3途径与αvβ-6整合素、哺乳动物靶标雷帕霉素(MTor)和过氧化物酶体增殖物激活受体-γ(PPARγ)形成了一个复杂的信号网络，具有广泛的串扰和对纤维化发展的强烈作用。本研究观察了转化生长因子β、Smad3、αvβ6整合素、mTOR和PPARγ在2，4，6-三硝基苯磺酸(TnBS)诱导的Smad3野生型(WT)和空白小鼠结肠纤维化中的表达。经TNBS处理的Smad3WT小鼠出现明显的结直肠纤维化，表现为转化生长因子β、Smad3、αvβ6和mTOR表达上调，PPARγ表达降低。另一方面，经TnBS类似处理的Smad3阴性小鼠未出现纤维化，转化生长因子β、Smad3、αvβ6和mTOR的表达很低甚至完全缺失，而PPARγ的表达显著升高。同时，α-平滑肌肌动蛋白(激活的肌成纤维细胞的标志物)、I-III型胶原和结缔组织生长因子(转化生长因子β/Smad3诱导的细胞外基质蛋白的下游效应因子)的表达在接受TNBS治疗的Smad3WT小鼠中比未接受TNBS治疗的小鼠上调。这些初步结果提示，在肠纤维化的发展过程中，这些促纤维化分子之间可能存在相互作用。
A simultaneous action of several pro-fibrotic mediators appears relevant in the development of fibrosis. There are evidences that transforming growth factor-β (TGF-β)/Smad3 pathway forms with αvβ6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-γ (PPARγ) a complex signalling network with extensive crosstalk and strong effects on fibrosis development. The present study evaluated the expression of TGFβ, Smad3, αvβ6 integrin, mTOR and PPARγ in 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colorectal fibrosis in Smad3 wild-type (WT) and null mice. Smad3 WT mice treated with TNBS developed a marked colorectal fibrosis and showed a concomitant up-regulation of TGFβ, Smad3, αvβ6 and mTOR and a reduction of PPARγ expression. On the other hand, Smad3 Null mice similarly treated with TNBS did not develop fibrosis and showed a very low or even absent expression of TGFβ, Smad3, αvβ6 and mTOR and a marked over-expression of PPARγ. At the same time the expression of α-smooth muscle actin (a marker of activated myofibroblasts), collagen I-III and connective tissue growth factor (a downstream effector of TGFβ/Smad3-induced extracellular matrix proteins) were up-regulated in Smad3 WT mice treated with TNBS compared to Null TNBS-treated mice. These preliminary results suggest a possible interaction between these pro-fibrotic molecules in the development of intestinal fibrosis.
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2.3
作者：
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