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Cellular and molecular mechanisms of intestinal fibrosis

World Journal of Gastroenterology 2012年第28期18卷 3635-3661页

作者： Silvia Speca Ilaria Giusti Florian Rieder Giovanni Latella Gastroenterology Unit Department of Internal Medicine and Public Health University of L'Aquila 67100 L'Aquila Italy Department of Gastroenterology and Hepatology Lerner Research Institute Cleveland Clinic Foundation Cleveland OH 73051 United States

fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.

关键词： Inflammatory bowel disease intestinal fibrosis Extracellular matrix Molecular mediators Myofibroblasts Inflammatory cells Epithelial cells Mesenchymal cells Endothelial cells

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Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis

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World Journal of Clinical Cases 2022年第22期10卷 7674-7685页

作者： Lie Zheng Yong-Yi Ji Yan-Cheng Dai Xin-Li Wen Shi-Cheng Wu Department of Gastroenterology Shaanxi Hospital of Traditional Chinese MedicineShaanxi Provincial Hospital of Traditional Chinese MedicineXi’an 730000Shaanxi ProvinceChina Department of Neurology Xi’an Hospital of Traditional Chinese MedicineXi’an 710021Shaanxi ProvinceChina Department of Gastroenterology Shanghai Traditional Chinese Medicine Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai 200082China Department of Gastroenterology Shaanxi Hospital of Traditional Chinese MedicineXi’an 710003Shaanxi ProvinceChina Department of Proctology Gansu Academy of Traditional Chinese MedicineGanSu Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina

BACKGROUND Inflammatory bowel disease(IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine(TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmerictrisomes on inducing mucosal healing in IBD is not *** To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking *** The chemical constituents and targets of Rhizoma zedoary and Rhizoma sanarum were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A “zedoary turmeric-trisomes-chemical composition-target-disease” network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the “Network Analysis” plug-in. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the “zedoary turmeric-trisomes-chemical composition-target-dis

关键词： Network pharmacology Molecular docking Zedoary turmeric trisomes Inflammatory bowel disease intestinal fibrosis

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Inhibiting Effect and Mechanism of Aconitum tanguticum(Maxim.) Stapf on intestinal fibrosis of CCD-18Co Cells

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World Journal of Traditional Chinese Medicine 2024年第3期10卷 354-362页

作者： Qin-Dan Cui Li-Dan Shen Yuan Bai Muhammad Azhar Jun Deng Xian-Ju Huang Hai-Ying Tong Department of Pharmacy Ethnopharmacology Level 3 Laboratory National Administration of Traditional Chinese Medicine School of Pharmaceutical SciencesSouth-Central Minzu University Department of Biosciences COMSATS University IslamabadSahiwal Campus Department of EthnomedicineInstitute of Ethnic Medicines School of Traditional Chinese Medicine Beijing University of Chinese Medicine

Objective: The objective of the study was to explore the potential signaling mechanism of Aconitum tanguticum(Maxim.) Stapf(ATS) and its impact on intestinal fibrosis in vitro. Methods: Network pharmacology was used to screen the active components of ATS and predict their potential targets in intestinal fibrosis. The protein–protein interaction network graph was constructed using drug–disease intersection targets retrieved from the Search Tool for Retrieval of Interacting Genes/Proteins database. The network diagram was analyzed using Cytoscape 3.6.1'stopology function. The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted using the database for annotation, visualization, and integrated discovery platform. intestinal fibroblast model in vitro was constructed using transforming growth factor-β1(TGF-β1)-induced CCD-18Co cells. Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to verify the network pharmacology-predicted antifibrotic signaling pathway of ATS and the traditional antifibrotic signaling pathway. Results: Network pharmacology revealed that there were 19 active components in ATS, suggesting that ATS could be involved in the regulation of mitogen-activated protein kinase 1(MAPK1), PIK3CA, MAPK3, and other important targets that are present in cancer pathways, including proteoglycans, infiuenza A, and phosphatidylinositol-3-kinase(PI3K)-protein kinase B(Akt) signaling pathways. The results of quantitative reverse transcription-polymerase chain reaction(qRT-PCR) demonstrated that 0.1–1 μg/mL ATS may suppress tissue inhibitor of metalloproteinase 1, collagen I, and alpha-smooth muscle actin expression levels. The expression of the TGF-β/suppressor of the mother against decapentaplegic(Smad) and PI3K/Akt signaling pathways was controlled by ATS. In addition, ATS inhibited the PI3K/Akt pathway by reducing the expression of MAPK1, HSP90AA1, and PIK3CA. Conclusions: It has been confirmed that AT

关键词： Aconitum tanguticum (Maxim.) Stapf CCD-18Co cells intestinal fibrosis network pharmacology transforming growth factor-β/suppressor of the mother against decapentaplegic signal pathway

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Visceral adipose volume is correlated with surgical tissue fibrosis in Crohn’s disease of the small bowel

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Gastroenterology Report 2022年第1期10卷 451-459页

作者： Gang Yuan Yao He Qing-Hua Cao Mi-Mi Tang Zong-Lin Xie Yun Qiu Zhi-Rong Zeng Sui Peng Min-Hu Chen Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Pathology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Radiology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Institute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background This study explored the diagnostic performance of visceral adiposity to predict the degree of intestinal inflammation and *** The patients with Crohn’s disease(CD)who underwent surgical small bowel resection at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2007 and December 2017 were *** evaluated the intestinal imaging features of computed tomography enterography(CTE),including mesenteric inflammatory fat stranding,the target sign,mesenteric hypervascularity,bowel wall thickening,lymphadenopathy,stricture diameter,and maximal upstream *** used ***(Artificial Intelligence Kit,version 1.1)to calculate the visceral fat(VF)and subcutaneous fat(SF)volumes at the third lumbar vertebra *** tissue information was *** models were established based on the multivariate regression analysis results,and their effectiveness was evaluated by area under the curve(AUC)and decision curve *** Overall,48 patients with CD were included in this *** abdominal VF/SF volume ratio(odds ratio,1.20;95%confidence interval,1.05–1.38;P=0.009)and the stenosis diameter/upstream intestinal dilatation diameter(ND)ratio(odds ratio,0.90;95%confidence interval,0.82–0.99;P=0.034)were independent risk factors for the severe fibrosis of the small *** AUC values of the VF/SF ratio,the ND ratio,and their combination were 0.760,0.673,and 0.804,*** combination of the VS/SF volume ratio and ND ratio achieved the highest net benefit on the decision *** The VF volume on CTE can reflect intestinal *** combination of the VF/SF volume ratio and ND ratio of CD patients assessed using CTE can help predict severe fibrosis stenosis of the small intestine.

关键词： Crohn’s disease intestinal fibrosis visceral fat computed tomography enterography

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Role of gut microbiota in Crohn’s disease pathogenesis:Insights from fecal microbiota transplantation in mouse model

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World Journal of Gastroenterology 2024年第31期30卷 3689-3704页

作者： Qiang Wu Lian-Wen Yuan Li-Chao Yang Ya-Wei Zhang Heng-Chang Yao Liang-Xin Peng Bao-Jia Yao Zhi-Xian Jiang Geriatric Surgery of Department of General Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and *** To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in *** intestinal tissue and MAT were collected from 12 patients with *** manifestations and protein expression levels were analyzed to determine lesion *** samples were collected from five recently treated CD patients and five control subjects and transplanted into *** intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control *** Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota *** microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD ***,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and ***,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced *** Gut microbiota play a critical role in the histopathology of *** MAT and creeping fat may therefore have potential in the treatment of patients with CD.

关键词： Mesenteric adipose tissue Crohn’s disease Fecal microbiota transplantation intestinal fibrosis intestinal barrier

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Resveratrol inhibits collagen Ⅰ synthesis by suppressing IGF-1R activation in intestinal fibroblasts

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World Journal of Gastroenterology 2014年第16期20卷 4648-4661页

作者： Ping Li Mei-Lan Liang Ying Zhu Yao-Yao Gong Yun Wang Ding Heng Lin Lin Department of Gastroenterology First Affiliated Hospital of Nanjing Medical University Nanping First Hospital Affiliated to Fujian Medical University

AIM: To investigate whether resveratrol (3,4,5-trihydroxy-trans-stilbene) inhibits collagen I synthesis induced by insulin growth factor-1 (IGF-1) in intestinal fibroblasts, and to explore the possible molecular mecha... 详细信息

关键词： intestinal fibrosis Insulin-like growth factor-1 Resveratrol Silent information regulator 1 Fibroblasts

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Contribution of gut microbiota to the development of Crohn's disease:Insights gained from fecal microbiota transplantation studies in mice

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World Journal of Gastroenterology 2024年第41期30卷 4514-4517页

作者： Jin Wang Yao Meng Zhi-Guo Guo Department of Gastroenterology Suzhou Hospital of Anhui Medical UniversitySuzhou 234000Anhui ProvinceChina

We would like to present some new thoughts on the publication in the journalpublished in August 2024 in World Journal of *** specificallyfocused on the alterations in the intestinal tract,mesenteric adipose tissue(MAT),and systemic inflammatory changes in mice following fecal flora transplantationinto a mouse model of Crohn's disease(CD).Accumulating evidence suggests thatthe occurrence of CD is influenced by environmental factors,host immune status,genetic susceptibility,and flora *** microbiota-based intervention,fecal microbiota transplantation,has emerged as a potential treatment option *** MAT is considered a"second barrier"around the inflamed *** between gut microbes and inflammatory changes in MAT has attractedconsiderable *** the study under discussion,the authors transplantedfetal fecal microorganisms from patients with CD and clinically healthy donors,respectively,into 2,4,6-trinitrobenzene sulfonic acid-induced CD *** explored the complex interplay between MAT,creeping fat,inflammation,and intestinal flora in CD by evaluating intestinal and mesenteric lesions,along with the systemic inflammatory state in the *** article providesseveral important ***,the transplantation of intestinal flora holdssignificant potential as a therapeutic strategy for CD,offering hope for patientswith ***,it presents a novel approach to the diagnosis and treatment ofCD:The inflammatory response in CD could potentially be assessed throughpathological or imaging changes in the MAT,and CD could be treated bytargeting the inflammation of the MAT.

关键词： Fecal microbiota transplantation Mesenteric adipose tissue Creeping fat Inflammation intestinal fibrosis Crohn's disease

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