Proinflammatory cytokines induce crosstalk between colonic epithelial cells and subepithelial myofibroblasts: Implication in intestinal fibrosis

Drygiannakis, Ioannis; Valatas, Vassilis; Sfakianaki, Ourania; Bourikas, Leonidas A.; Manousou, Pinelopi; Kambas, Konstantinos; Ritis, Konstantinos; Kolios, George; Kouroumalis, Elias

doi:10.1016/j.crohns.2012.04.008

Cited by 72 publications

(64 citation statements)

References 38 publications

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“…We examined in vitro the effect of phospholipids on the collagen production and proliferation/migration of myofibroblasts. We have previously demonstrated that TGFb1 can increase both collagen production and myofibroblast migration [22,41]. In this study, treatment of myofibroblasts with various concentrations of phospholipids resulted in a statistical significant reduction of both basal and TGFb1-induced collagen production.…”

Section: Discussionmentioning

confidence: 80%

“…Myofibroblast migration was assessed in vitro with the wound healing scratch assay that resembles wound healing and is dependent on myofibroblast migration, as previously described [21,22]. Forty-eight hours before the assay, the FBS concentration in the media was gradually reduced from 10%e 5% to minimize the contribution of proliferation.…”

Section: Wound Healing Scratch Assaymentioning

confidence: 99%

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Intraperitoneal application of phospholipids for the prevention of postoperative adhesions: a possible role of myofibroblasts

Fotiadis

Filidou

Arvanitidis

et al. 2015

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 80%

Section: Wound Healing Scratch Assaymentioning

confidence: 99%

Intraperitoneal application of phospholipids for the prevention of postoperative adhesions: a possible role of myofibroblasts

Fotiadis

Filidou

Arvanitidis

et al. 2015

Journal of Surgical Research

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“…Recently, we have shown that stimulation of human SEMFs with proinflammatory cytokines results in production of tumor necrosis factor (TNF)-like ligand 1A (TL1A), a molecule recently implicated in both T-cell differentiation and intestinal fibrosis [33]. Concerning their possible participation in post-inflammatory intestinal fibrosis, SEMFs have been found to respond to proinflammatory and profibrotic cytokines, such as IL-17A [34] and TGF-β [35], by increasing production of collagen and MMPs. Finally, we have shown that conditioned medium from epithelial cell cultures stimulated with proinflammatory cytokines can enhance SEMF migration, and production of collagen and MMPs, suggesting the existence of a crosstalk between SEMFs and overlying epithelial cells during intestinal inflammation that can generate profibrotic responses [35].…”

Section: The Activated Myofibroblastmentioning

confidence: 99%

Stromal and immune cells in gut fibrosis: the myofibroblast and the scarface

Valatas

Filidou

Drygiannakis

et al. 2017

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Post-inflammatory scarring is the end-result of excessive extracellular matrix (ECM) accumulation and tissue architectural destruction. It represents a failure to effectively remodel ECM and achieve proper reinstitution and healing during chronic relapsing inflammatory processes. Scarring may affect the functionality of any organ, and in the case of inflammatory bowel disease (IBD)-associated fibrosis leads to stricture formation and often surgery to remove the affected bowel. The activated myofibroblast is the final effector cell that overproduces ECM under the influence of various mediators generated by an intense interplay of classic and non-classic immune cells. This review focuses on how proinflammatory mediators from various sources produced in different stages of intestinal inflammation can form profibrotic pathways that eventually lead to tissue scarring through sustained activation of myofibroblasts.

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“…This has important implications on the crosstalk between subepithelial myofibroblasts and epithelial cells that regulate each other’s function. Epithelial cells respond to the paracrine stimuli from myofibroblasts to increase their TGF-β1 and TIMP-1 expression 42 .…”

Section: Cellular Basis Of Fibrosismentioning

confidence: 99%

Mechanisms That Mediate the Development of Fibrosis in Patients With Crohnʼs Disease

Li¹,

Kuemmerle

2014

Inflammatory Bowel Diseases

104

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Crohn’s disease is complicated by the development of fibrosis and stricture in ~30–50% of patients over time. The pathogenesis of fibrostenotic disease is multifactorial involving the activation of mesenchymal cells by cytokines, growth factors and other mediators released by immune cells, epithelial cells and mesenchymal cells themselves. Transforming growth factor-β (TGF-β), a key activator of mesenchymal cells, is central to the process of fibrosis and regulates numerous genes involved in the disordered wound healing including collagens, and other extracellular matrix proteins, connective tissue growth factor (CTGF), and insulin-like growth factors (IGFs). The activated mesenchymal compartment is expanded by recruitment of new mesenchymal cells via epithelial to mesenchymal transition, endothelial to mesenchymal transition and invasion of circulating fibrocytes. Cellular hyperplasia and increased extracellular matrix (ECM) production, particularly collagens, from fibroblasts, myofibroblasts and smooth muscle cells add to the disturbed architecture and scarring on the intestine. ECM homeostasis is further disrupted by alterations in the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in the gut. Among the 163 susceptibility genes identified that contribute to susceptibility in IBD mutations in NOD2/CARD15, innate immune system components, and autophagy jointly contribute to the activation of mesenchymal cells and pathogenesis of fibrosis in this polygenic disorder. Numerous growth factorscytokinesand other mediators. The review focuses on the molecular mechanism that regulate mesenchymal cell function, particularly smooth muscle cells, the largest compartment of mesenchyme in the intestine, that lead to fibrosis in Crohn’s disease.

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Proinflammatory cytokines induce crosstalk between colonic epithelial cells and subepithelial myofibroblasts: Implication in intestinal fibrosis

Abstract: Our study indicates that colonic epithelial cells may respond to an inflammatory milieu by inducing myofibroblast functions similar to those observed during intestinal fibrosis.

Cited by 72 publications

References 38 publications

Intraperitoneal application of phospholipids for the prevention of postoperative adhesions: a possible role of myofibroblasts

Intraperitoneal application of phospholipids for the prevention of postoperative adhesions: a possible role of myofibroblasts

Stromal and immune cells in gut fibrosis: the myofibroblast and the scarface

Mechanisms That Mediate the Development of Fibrosis in Patients With Crohnʼs Disease

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