Treatment of intestinal fibrosis in experimental inflammatory bowel disease by the pleiotropic actions of a local Rho kinase inhibitor

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 153; no. 4; pp. 1054 - 1067
• Main Authors: Holvoet, Tom, Devriese, Sarah, Castermans, Karolien, Boland, Sandro, Leysen, Dirk, Vandewynckel, Yves-Paul, Devisscher, Lindsey, Van den Bossche, Lien, Van Welden, Sophie, Dullaers, Melissa, Vandenbroucke, Roosmarijn E, De Rycke, Riet, Geboes, Karel, Bourin, Arnaud, Defert, Olivier, Hindryckx, Pieter, De Vos, Martine, Laukens, Debby
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017
• Subjects: Adoptive Transfer; Animals; Autophagy - drug effects; Case-Control Studies; Colitis; Collagen - metabolism; Dextran Sulfate; Disease Models, Animal; Enzyme Activation; Epithelial-to-Mesenchymal Transition; Fibrosis; Gastroenterology and Hepatology; Humans; Ileum - drug effects; Ileum - enzymology; Ileum - immunology; Ileum - pathology; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - pathology; Inflammatory Bowel Diseases - prevention & control; Interleukin-6 - metabolism; Intestinal Obstruction - chemically induced; Intestinal Obstruction - enzymology; Intestinal Obstruction - pathology; Intestinal Obstruction - prevention & control; Male; Matrix Metalloproteinases - metabolism; Mesenchymal Cells; Mice, Inbred C57BL; Myofibroblasts - drug effects; Myofibroblasts - enzymology; Myofibroblasts - immunology; Myofibroblasts - pathology; p38 Mitogen-Activated Protein Kinases - metabolism; Protein Kinase Inhibitors - pharmacology; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Signal Transduction - drug effects; Stenosis; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Time Factors; Tissue Culture Techniques; colitis; 2, 4, 6-trinitrobenzenesulfonic acid; MLC; autophagy-related 16 like 1; alpha smooth muscle actin; MTT; MPO; TNF; UC; CTGF; myosin light chain; ulcerative colitis; human intestinal fibroblasts; IL; DSS; dextran sulfate sodium; lactate dehydrogenase; EMT; inflammatory bowel disease; epithelial-to-mesenchymal transition; connective tissue growth factor; MMP; severe combined immunodeficient; TGF; lipopolysaccharide; ROCK; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; IBD; stenosis; SCID; LPS; IFN; LDH; MCP1; myocardin-related transcription factor; interleukin; Crohn’s disease; CD; HIF; myeloperoxidase; interferon; TNBS; ECM; Rho-associated coiled-coil-containing protein kinase; MRTF; tumor necrosis factor; ATG16L1; monocyte chemo-attractant protein 1; LC; αSMA; microtubule-associated protein light chain; matrix metalloproteinase; transforming growth factor; mesenchymal cells; extracellular matrix; Stenosis; IP; qRT-PCR; Epithelial-to-Mesenchymal Transition; Colitis; Mesenchymal Cells

Abstract Background Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn’s disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-eff...