Proteomics Highlights Common and Distinct Pathophysiological Processes Associated with Ileal and Colonic Ulcers in Crohn’s Disease

2019 ◽  
Vol 14 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Nicolas Pierre ◽  
Catherine Salée ◽  
Charlotte Massot ◽  
Noëlla Blétard ◽  
Gabriel Mazzucchelli ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Mesenchymal Transition ◽  
Colonic Disease ◽  
Differential Proteomics ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Colonic Ulcer ◽  
Endoplasmic Reticulum Protein

Abstract Background and Aims Based on genetics and natural history, Crohn’s disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. Methods The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn’s disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry. Results In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial–mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges. Conclusion This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn’s disease patients. This could constitute a first step toward the development of gut segment–specific diagnostic markers and therapeutics.

scholarly journals Herbs-Partitioned Moxibustion Combined with Acupuncture Inhibits TGF-β1-Smad-Snail-Induced Intestinal Epithelial Mesenchymal Transition in Crohn’s Disease Model Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yin Shi ◽  
Tao Li ◽  
Jing Zhou ◽  
Yuwei Li ◽  
Liu Chen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Cell Marker ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis

Crohn’s disease may cause excessive damage and repair in the intestinal epithelium due to its chronic relapsing intestinal inflammation. These factors may initiate the TGF-β 1-Smad pathway to activate the transcription factor of Snail, and the Snail-mediated pathway promotes the transformation of intestinal epithelial cells to mesenchymal cells, leading to intestinal fibrosis. Acupuncture and moxibustion have been demonstrated to prevent intestinal fibrosis in Crohn’s disease. However, it is not clear whether acupuncture and moxibustion can inhibit intestinal epithelial mesenchymal transformation in Crohn’s disease by affecting the TGF-β 1-Smad-Snail pathway. This study indicated that abnormal increased expressions of TGFβ1, TβR2, Smad3, and Snail were significantly downregulated by herbs-partitioned moxibustion at Tianshu (ST25) and Qihai (RN6) and acupuncture at Zusanli (ST36) and Shangjuxu (ST37). In addition, protein and mRNA levels of E-cadherin, the epithelial cell marker, were significantly increased. Protein and mRNA levels of fibronectin, the mesenchymal cell marker, were decreased in the intestinal tissue. Moreover, the number of mesenchymal cells in the intestinal mucosa can be reversely transformed to intestinal epithelial cells. Therefore, herbs-partitioned moxibustion combined with acupuncture can prevent intestinal epithelial mesenchymal transition by inhibiting abnormal expression of TGFβ1, TβR2, Smad3, and Snail in the TGF-β1-Smad-Snail pathway in Crohn’s disease.

scholarly journals LINC01272 Activates Epithelial-Mesenchymal Transition Through miR-153-5p in Crohn’s Disease

2021 ◽  
Author(s):  
Lin Fang ◽  
Mengcheng Hu ◽  
Fei Xia ◽  
wenxia Bai
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Reporter Assays ◽  
Tgf Β1

Abstract Background: Long non-coding RNAs (lncRNAs) have different functions in different diseases. There is seldom research on the functions of lncRNAs in Crohn’s disease (CD). By RNA-seq technology, we identify a lncRNA associated with Crohn's disease. However, the mechanism of lncRNA regulation remains unknown. This study aimed to determine the association of LINC01272 with epithelial cell-mesenchymal transition and the underlined mechanism in CD.Methods: RNA is detected by qRT-PCR. Interaction of protein and RNA was determined by RNA binding protein immunoprecipitation. Luciferase reporter assays were used to detect the targeted miRNA of LINC01272. Tissue fibrosis was observed by Masson and HE staining. The protein expression is determined by western blot and immunofluorescence. Results: LINC01272 was highly expressed in patients with CD. Knockdown of LINC01272 inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT). Additionally, LINC01272 regulated TGF-β1 induced EMT by miR-153-5p axis and knockdown of LINC01272 inhibited EMT in the CD mice in vivo. Conclusion: LINC01272 activated epithelial-mesenchymal transition through miR-153-5p in CD.

scholarly journals MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenrui Duan ◽  
Shirley Tang ◽  
Li Gao ◽  
Kathleen Dotts ◽  
Andrew Fink ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Epithelial Mesenchymal Transition ◽  
Micro Rna ◽  
Negative Regulator ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Tissue Samples ◽  
Lung Cancers ◽  
Mesenchymal Transition ◽  
Micro Rnas

AbstractThe Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This pathway is involved in repairing damaged DNA through homologous recombination. Cancers with a defective FA pathway are expected to be more sensitive to cross-link based therapy or PARP inhibitors. To evaluate downstream effectors of the FA pathway, we studied the expression of 734 different micro RNAs (miRNA) using NanoString nCounter miRNA array in two FA defective lung cancer cells and matched control cells, along with two lung tumors and matched non-tumor tissue samples that were deficient in the FA pathway. Selected miRNA expression was validated with real-time PCR analysis. Among 734 different miRNAs, a cluster of microRNAs were found to be up-regulated including an important cancer related micro RNA, miR-200C. MiRNA-200C has been reported as a negative regulator of epithelial-mesenchymal transition (EMT) and inhibits cell migration and invasion by promoting the upregulation of E-cadherin through targeting ZEB1 and ZEB2 transcription factors. miRNA-200C was increased in the FA defective lung cancers as compared to controls. AmpliSeq analysis showed significant reduction in ZEB1 and ZEB2 mRNA expression. Our findings indicate the miRNA-200C potentially play a very important role in FA pathway downstream regulation.

Improvement of a ‘Leaky' Intestinal Barrier

2017 ◽  
Vol 35 (1-2) ◽  
pp. 21-24 ◽  
Author(s):  
Eduard F. Stange
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Barrier ◽  
Bacterial Attachment ◽  
Phase Iii ◽  
Colonic Disease ◽  
Mucus Layer ◽  
Tissue Destruction ◽  
Liquid Form ◽  
Mucus Production

In Crohn's disease, the mucus layer appears to be defective in terms of low defensin levels and lack of antibacterial activity. These deficiencies actually explain the Montreal phenotypes and the stable localization of disease in the terminal ileum with low α-defensins from Paneth cells and/or low β-defensins in colonic disease, respectively. Conversely, in ulcerative colitis (UC) the defensin production is normal or even induced, but the mucus layer is thinner and patchy, more in the liquid form and also chemically altered so that antibacterial peptides are not retained and lost into the luminal bacterial bulk. Therefore, both barrier problems allow slow bacterial attachment and invasion, ultimately triggering the massive response of adaptive immunity and tissue destruction. Therefore, leakiness should refer to the antibacterial barrier and not to the general barrier against small molecules, such as mannitol or lactulose, which are not antigenic. The most promising approach in UC seems to be the use of probiotics or the natural compound lecithin as a stabilizer of mucus structure to enhance the barrier. While a phase II study has yielded positive results, the results of the ongoing phase III study are eagerly awaited. It is quite possible that the protective effect of smoking in UC is related to mucus production in the colon also, but this is not an option. Another alternative would be to shift cell differentiation in the colon towards goblet cell; the relevant differentiation factors are known. In Crohn's disease, the direct oral application of defensins might be effective if release and binding to the mucus are achieved. In the experimental colitis model, this works quite well. In conclusion, in a situation where enthusiasm about so-called biologics is declining due to loss of response over time, searching for the primary defects in inflammatory bowel disease and treating them may well be worthwhile, although it is unlikely to provide rapid relief.

scholarly journals Proteomic analysis-based discovery of a novel biomarker that differentiates intestinal Behçet’s disease from Crohn’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jihye Park ◽  
Daeun Jeong ◽  
Youn Wook Chung ◽  
Seunghan Han ◽  
Da Hye Kim ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Proteomic Analysis ◽  
Behcet’S Disease ◽  
Differentially Expressed ◽  
Tandem Mass ◽  
Intestinal Behçet’S Disease ◽  
Tissue Samples ◽  
Intestinal Behcet’S Disease ◽  
Intestinal Behçet's Disease

AbstractIntestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific diagnostic tests to differentiate them. We used a proteomic approach to discover novel diagnostic biomarkers specific to intestinal BD. Colon mucosa tissue samples were obtained from patients with intestinal BD or CD using colonoscopy-guided biopsy of the affected bowel. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Using TMT/LC–MS/MS-based proteomic quantification, we identified 39 proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed higher intensity in the IHC staining of intestinal BD tissues than in CD tissues. The serum MGAM level was higher in intestinal BD patients. Proteomic analysis revealed that some proteins were differentially expressed in patients with intestinal BD compared with those with CD. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker.

scholarly journals Erythema Nodosum and Pyoderma Gangrenosum in 50 Patients with Crohn’s Disease

2005 ◽  
Vol 19 (10) ◽  
pp. 603-606 ◽  
Author(s):  
Hugh J Freeman
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pyoderma Gangrenosum ◽  
Complex Disease ◽  
Erythema Nodosum ◽  
Colonic Disease ◽  
Detection Rates ◽  
Dependent Effect ◽  
Age Dependent ◽  
Dermatological Disorders

Erythema nodosum and pyoderma gangrenosum may occur in Crohn's disease. In the present evaluation of consecutive patients with Crohn's disease spanning more than two decades, erythema nodosum was seen in 45 patients and pyoderma gangrenosum was seen in seven patients. Forty-one of 566 women (7.2%) and nine of 449 men (2.0%) were affected. Of these, 45 (4.4%) had erythema nodosum and seven (0.7%) had pyoderma gangrenosum, including two (0.2%) with both dermatological disorders at different times during their clinical courses. Recurrent erythema nodosum was also detected in nine patients (20%) including eight women, while recurrent pyoderma gangrenosum was seen in two patients (28.6%). There was an age-dependent effect on the appearance of erythema nodosum in women, with the highest percentages seen in those younger than 20 years of age. Detection rates for erythema nodosum in women only approached the low mens' rates in Crohn's disease at older than 40 years of age. Most patients with these dermatological disorders had colonic disease with or without ileal involvement as well as complex disease, usually with penetrating complications. The present study documents a sex-based and age-dependent effect on the clinical expression of erythema nodosum in Crohn's disease. This suggests that some components of the inflammatory process in Crohn's disease may be modulated by estrogen-mediated events, particularly in adolescents and young adults.

scholarly journals P058 Proteomic analysis-based discovery of a novel biomarker that differentiates intestinal Behçet’s disease from Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S164-S165
Author(s):  
J Park ◽  
J Daeun ◽  
C Youn Wook ◽  
C Jae Hee ◽  
R Ji-Hwan
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Proteomic Analysis ◽  
Differentially Expressed ◽  
Tandem Mass ◽  
Diagnostic Biomarker ◽  
Intestinal Behçet’S Disease ◽  
Tissue Samples ◽  
Intestinal Behcet’S Disease ◽  
Intestinal Behçet's Disease

Abstract Background Intestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific pathognomonic clinical, laboratory, or histological diagnostic tests to differentiate intestinal BD from CD. We used a proteomic approach to discover a novel diagnostic biomarker specific to intestinal BD. Methods The colon mucosa tissue samples were obtained using colonoscopy-guided biopsy of the affected bowel from patients with intestinal BD or CD at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Results A total of 3,266 proteins were identified using TMT/LC-MS/MS-based proteomic quantification, including 39 candidate proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed significantly higher intensity in the IHC staining of the intestinal BD tissues than that of CD tissues. Furthermore, the serum MGAM level was significantly higher in patients with intestinal BD than in patients with CD. Conclusion Our proteomic analysis revealed that some proteins were differentially expressed in intestinal BD patients compared to CD patients. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker in the differentiation of intestinal BD from CD.

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