20.500.12556/RUL-128790 Pathology of fibrosis in Crohn's disease - contribution to understanding its pathogenesis Background: Despite significant progress in the research of fibrosis in various organs, fibrosis remains a poorly understood complication of Crohn's disease (CD). We analyzed pathologic features of fibrosis and inflammation in CD and compared them with the normal bowel, aiming to clarify whether fibrosis in CD pathogenetically resembles fibrosis in other organs. Methods: Resection specimens from 30 patients with CD were included. Normal bowel from resection specimens of colorectal carcinoma was used for comparison. Trichrome Masson staining, immunohistochemistry for α-smooth muscle actin, fibroblast activation protein, CD34 and erg, in situ hybridization for TGF-β1 and analysis of selected fibrosis-related microRNAs were performed. Results: In normal bowel, CD34-positive fibroblasts/pericytes were detected in the submucosa and subserosa, particularly around blood vessels. In CD, fibrosis prevailed in the submucosa and subserosa, together with proliferation of myofibroblasts and disappearance of CD34-positive fibroblasts/pericytes. TGF-β1 was present in the lamina propria in normal bowel and CD, and in deeper parts of the bowel wall in CD. MicroRNAs miR-29c, miR-155 miR-150, and miR-155, which have been demonstrated to contribute to fibrosis in various organs, showed significant deregulation in CD. Conclusions: Distribution of fibroblasts/pericytes in the submucosa and subserosa of normal bowel, their disappearance in fibrosis in CD, together with the appearance of myofibroblasts, suggest that fibroblasts/pericytes are the most likely source of myofibroblasts in CD. Furthemore, fibrosis-related microRNAs showed deregulation in fibrotic areas. Pathogenesis of fibrosis in CD is thus comparable to fibrosis in other organs, in which myofibroblasts are the key effector cells, and pericytes have emerged as the main origin of myofibroblasts. Fibrosis in CD should be regarded as a result of (over)response of the bowel wall to the presence of inflammation in deep structures of the bowel wall, presenting another example of a common pathogenetic pathway of fibrosis development. Crohn's disease fibrosis stenosis pathology pathogenesis Crohnova bolezen fibroza stenoza patologija patogeneza true false true Angleški jezik Slovenski jezik Članek v reviji 2021-07-29 15:36:50 2021-07-29 15:36:52 2022-09-07 04:17:13 0000-00-00 00:00:00 2020 0 0 11 str. Vol. 7, art. 167 May 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616 2296-858X 10.3389/fmed.2020.00167 23893507 RAZ_Zidar_Nina_2020.pdf RAZ_Zidar_Nina_2020.pdf 1 67E115459FA803BB21EBDC08145EEB57 2ba8cfe753f2d373d70256a760ff2fd070bc15ca670e1badc6ade3414dc8e258 de44ea82-f071-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=145673 https://www.frontiersin.org/articles/10.3389/fmed.2020.00167/full 0 7bbfd4bd-f072-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=145674 Medicinska fakulteta 0 0 0