Molecular Activity of Inflammation and Epithelial-Mesenchymal Transition in the Microenvironment of Ulcerative Colitis
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Background/Aims: The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions: Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions
Abstract
Background/Aims: The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions: Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions
참고문헌 (45)
- Conrad K, "Diagnosis and classification of ulcerative colitis", Autoimmun Rev, 13, pp.463~466 (2014)
- Sood A, "Endoscopy for assessment of mucosal healing in ulcerative colitis : time bound or response guided?", Intest Res, 20, pp.297~302 (2022)
- Colombel JF, "Early mucosal healing with infliximab is associated with improved longterm clinical outcomes in ulcerative colitis", Gastroenterology, 141, pp.1194~1201 (2011)
- Arai M, "The ulcerative colitis endoscopic index of severity is useful to predict mediumto long-term prognosis in ulcerative colitis patients with clinical remission", J Crohns Colitis, 10, pp.1303~1309 (2016)
- Zahn A, "Transcript levels of different cytokines and chemokines correlate with clinical and endoscopic activity in ulcerative colitis", BMC Gastroenterol, 9, pp.13~ (2009)
- Arkteg CB, "Mucosal gene transcription of ulcerative colitis in endoscopic remission", Scand J Gastroenterol, 55, pp.139~147 (2020)
- Rieder F, "Mechanisms of tissue remodeling in inflammatory bowel disease", Dig Dis, 31, pp.186~193 (2013)
- Choi YJ, "Helicobacter pylori. Volume 1", pp.275~291 (2016), Springer
- Marconi GD, "Epithelial-mesenchymal transition(EMT) : the type-2 EMT in wound healing, tissue regeneration and organ fibrosis", Cells, 10, pp.1587~ (2021)
- Zeisberg M, "Biomarkers for epithelial-mesenchymal transitions", J Clin Invest, 119, pp.1429~1437 (2009)
- Satsangi J, "The Montreal classification of inflammatory bowel disease : controversies, consensus, and implications", Gut, 55, pp.749~753 (2006)
- Lewis JD, "Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis", Inflamm Bowel Dis, 14, pp.1660~1666 (2008)
- Chateau T, "Histological remission in ulcerative colitis : under the microscope is the cure", Am J Gastroenterol, 115, pp.179~189 (2020)
- Marchal-Bressenot A, "Development and validation of the Nancy histological index for UC", Gut, 66, pp.43~49 (2017)
- Choi YJ, "Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells", Carcinogenesis, 36, pp.553~563 (2015)
- van Diest PJ, "A scoring system for immunohistochemical staining : consensus report of the task force for basic research of the EORTCGCCG. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Cooperative Group", J Clin Pathol, 50, pp.801~804 (1997)
- Andoh A, "Mucosal cytokine network in inflammatory bowel disease", World J Gastroenterol, 14, pp.5154~5161 (2008)
- Yeshi K, "Revisiting inflammatory bowel disease : pathology, treatments, challenges and emerging therapeutics including drug leads from natural products", J Clin Med, 9, pp.1273~ (2020)
- Hirano T, "IL-6 in inflammation, autoimmunity and cancer", Int Immunol, 33, pp.127~148 (2021)
- Dobre M, "Differential intestinal mucosa transcriptomic biomarkers for Crohn’s disease and ulcerative colitis", J Immunol Res, 2018, pp.9208274~ (2018)
- Krawiec P, "Serum interleukin 17A and interleukin 17F in children with inflammatory bowel disease", Sci Rep, 10, pp.12617~ (2020)
- Olsen T, "TH1 and TH17 interactions in untreated inflamed mucosa of inflammatory bowel disease, and their potential to mediate the inflammation", Cytokine, 56, pp.633~640 (2011)
- Petitpain N, "IL-17 inhibitors and inflammatory bowel diseases : a postmarketing study in Vigibase", Clin Pharmacol Ther, 110, pp.159~168 (2021)
- Zhao X, "Mobilization of epithelial mesenchymal transition genes distinguishes active from inactive lesional tissue in patients with ulcerative colitis", Hum Mol Genet, 24, pp.4615~4624 (2015)
- Lovisa S, "Role of epithelial-to-mesenchymal transition in inflammatory bowel disease", J Crohns Colitis, 13, pp.659~668 (2019)
- Wynn TA, "Mechanisms of fibrosis : therapeutic translation for fibrotic disease", Nat Med, 18, pp.1028~1040 (2012)
- Fernandez Vallone V, "LGR5 controls extracellular matrix production by stem cells in the developing intestine", EMBO Rep, 21, pp.e49224~ (2020)
- van der Flier LG, "Stem cells, self-renewal, and differentiation in the intestinal epithelium", Annu Rev Physiol, 71, pp.241~260 (2009)
- Yang J, "Guidelines and definitions for research on epithelial-mesenchymal transition", Nat Rev Mol Cell Biol, 21, pp.341~352 (2020)
- Gersemann M, "Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD", J Crohns Colitis, 6, pp.425~434 (2012)
- Li Y, "COX-2-PGE2signaling impairs intestinal epithelial regeneration and associates with TNF inhibitor responsiveness in ulcerative colitis", EBioMedicine, 36, pp.497~507 (2018)
- Girish N, "Persistence of Lgr5+colonic epithelial stem cells in mouse models of inflammatory bowel disease", Am J Physiol Gastrointest Liver Physiol, 321, pp.G308~G324 (2021)
- Younesi FS, "Myofibroblast markers and microscopy detection methods in cell culture and histology", Methods Mol Biol, 2299, pp.17~47 (2021)
- Flier SN, "Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis", J Biol Chem, 285, pp.20202~20212 (2010)
- gender-specific medicine in the gastrointestinal diseases. Volume 1, "Sex", pp.2022, Choi YH
- Klein SL, "Sex differences in immune responses", Nat Rev Immunol, 16, pp.626~638 (2016)
- Gundersen MD, "Fibrosis mediators in the colonic mucosa of acute and healed ulcerative colitis", Clin Transl Gastroenterol, 10, pp.e00082~ (2019)
- Gordon IO, "Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation", Aliment Pharmacol Ther, 47, pp.922~939 (2018)
- Cushing KC, "Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission", Aliment Pharmacol Ther, 51, pp.347~355 (2020)
- Yoon H, "Incremental benefit of achieving endoscopic and histologic remission in patients with ulcerative colitis : a systematic review and meta-analysis", Gastroenterology, 159, pp.1262~1275 (2020)
- Peyrin-Biaaroulet L, "Histologic remission : the ultimate therapeutic goal in ulcerative colitis?", Clin Gastroenterol Hepatol, 12, pp.929~934 (2014)
- de Frias Gomes CG, "Histological inflammation in the endoscopically uninflamed mucosa is associated with worse outcomes in limited ulcerative colitis", Inflamm Bowel Dis, 28, pp.350~357 (2022)
- Mosli MH, "Development and validation of a histological index for UC", Gut, 66, pp.50~58 (2017)
- Tsuda S, "Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint : role of macrophages and regulatory markers in disease severity", Pathol Int, 69, pp.260~271 (2019)
- Filardy AA, "The intestinal microenvironment shapes macrophage and dendritic cell identity and function", Immunol Lett, 253, pp.41~53 (2023)