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首页> 外文期刊>European Journal of Histochemistry >Localization of αυβ6 integrin-TGF-β1/Smad3, mTOR and PPARγ in experimental colorectal fibrosis
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Localization of αυβ6 integrin-TGF-β1/Smad3, mTOR and PPARγ in experimental colorectal fibrosis

机译:实验性结直肠纤维化中αυβ6整合素-TGF-β1/ Smad3,mTOR和PPARγ的定位

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摘要

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.
机译: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(TGF-β)/ Smad3途径与αvβ6整联蛋白,雷帕霉素的哺乳动物靶标(mTOR)和过氧化物酶体增殖物激活的受体-γ(PPARγ)形成复杂的信号网络,具有广泛的串扰和强大的影响。对纤维化的发展。本研究评估了TGFβ,Smad3,αvβ6整联蛋白,mTOR和PPARγ在2,4,6-三硝基苯磺酸(TNBS)诱导的Smad3野生型(WT)和无效小鼠的结肠直肠纤维化中的表达。 TNBS处理的Smad3 WT小鼠出现了显着的结直肠纤维化,并伴有TGFβ,Smad3,αvβ6和mTOR的上调以及PPARγ表达的降低。另一方面,类似地用TNBS处理的Smad3 Null小鼠没有发生纤维化,并且表现出TGFβ,Smad3,αvβ6和mTOR的表达非常低甚至不表达,并且PPARγ的表达明显过高。同时,在Smad3 WT中上调了α平滑肌肌动蛋白(活化的成肌纤维细胞的标志物),I-III胶原蛋白和结缔组织生长因子(TGFβ/ Smad3诱导的细胞外基质蛋白的下游效应子)的表达。与空TNBS处理的小鼠相比,用TNBS处理的小鼠。这些初步结果表明,这些促纤维化分子在肠道纤维化发展中可能存在相互作用。

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