PMID- 24441193 OWN - NLM STAT- MEDLINE DCOM- 20141022 LR - 20211203 IS - 2038-8306 (Electronic) IS - 1121-760X (Print) IS - 1121-760X (Linking) VI - 57 IP - 4 DP - 2013 Dec 4 TI - Localization of alphanubeta6 integrin-TGF-beta1/Smad3, mTOR and PPARgamma in experimental colorectal fibrosis. PG - e40 LID - 10.4081/ejh.2013.e40 [doi] LID - e40 AB - A simultaneous action of several pro-fibrotic mediators appears relevant in the development of fibrosis. There are evidences that transforming growth factor-beta (TGF-beta)/Smad3 pathway forms with alphavbeta6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma (PPARgamma) a complex signalling network with extensive crosstalk and strong effects on fibrosis development. The present study evaluated the expression of TGFbeta, Smad3, alphavbeta6 integrin, mTOR and PPARgamma 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 TGFbeta, Smad3, alphavbeta6 and mTOR and a reduction of PPARgamma 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 TGFbeta, Smad3, alphavbeta6 and mTOR and a marked over-expression of PPARgamma. At the same time the expression of alpha-smooth muscle actin (a marker of activated myofibroblasts), collagen I-III and connective tissue growth factor (a downstream effector of TGFbeta/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. FAU - Latella, G AU - Latella G AD - University of L'Aquila. giolatel@tin.it. FAU - Vetuschi, A AU - Vetuschi A FAU - Sferra, R AU - Sferra R FAU - Speca, S AU - Speca S FAU - Gaudio, E AU - Gaudio E LA - eng PT - Journal Article DEP - 20131204 PL - Italy TA - Eur J Histochem JT - European journal of histochemistry : EJH JID - 9207930 RN - 0 (Actins) RN - 0 (Antigens, Neoplasm) RN - 0 (Integrins) RN - 0 (PPAR gamma) RN - 0 (Smad3 Protein) RN - 0 (Smad3 protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - 0 (integrin alphavbeta6) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Actins/metabolism MH - Animals MH - Antigens, Neoplasm/*metabolism MH - Colon/drug effects/*pathology MH - Fibrosis MH - Integrins/*metabolism MH - Mice MH - PPAR gamma/*metabolism MH - Signal Transduction MH - Smad3 Protein/genetics/*metabolism MH - TOR Serine-Threonine Kinases/*metabolism MH - Transforming Growth Factor beta1/*metabolism MH - Trinitrobenzenesulfonic Acid PMC - PMC3896042 EDAT- 2014/01/21 06:00 MHDA- 2014/10/23 06:00 PMCR- 2013/12/04 CRDT- 2014/01/21 06:00 PHST- 2013/07/09 00:00 [received] PHST- 2013/11/04 00:00 [accepted] PHST- 2013/11/26 00:00 [revised] PHST- 2014/01/21 06:00 [entrez] PHST- 2014/01/21 06:00 [pubmed] PHST- 2014/10/23 06:00 [medline] PHST- 2013/12/04 00:00 [pmc-release] AID - ejh.2013.e40 [pii] AID - 10.4081/ejh.2013.e40 [doi] PST - epublish SO - Eur J Histochem. 2013 Dec 4;57(4):e40. doi: 10.4081/ejh.2013.e40.