Intestinal fibrosis

Latella, Giovanni; Rieder, Florian

doi:10.1097/mog.0000000000000363

Cited by 52 publications

(27 citation statements)

References 70 publications

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“…Intestinal inflammation triggers the activation of myofibroblasts that are central players in tissue repair, as they migrate into damaged tissue and control production and turnover of the extracellular matrix in support of all the other tissue-resident cell types. However, chronic inflammation leads to overactivation and proliferation of myofibroblasts that produce excessive amounts of ECM causing fibrosis [32,33]. Therefore, suppressing myofibroblast proliferation and/or ECM production is an important therapeutic target to control and prevent intestinal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Cui

Zhang

Leng

et al. 2020

Cells

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Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an anti-fibrotic compound available for the treatment of idiopathic pulmonary fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were cultured in the absence and presence of pirfenidone. Cell proliferation was measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell motility was monitored by live cell imaging. Cytotoxicity and cell viability were analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) assays. Gene expression of fibrosis markers was determined by quantitative reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) signaling was analyzed by Western blotting and type I collagen protein expression additionally by immunofluorescence microscopy. Pirfenidone dose-dependently inhibited p-hIF proliferation and motility, without inducing cell death. Pirfenidone suppressed mRNA levels of genes that contribute to extracellular matrix production, as well as basal and TGF-β1-induced collagen I protein production, which was associated with inhibition of the rapamycin-sensitive mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of intestinal fibroblasts and suppresses collagen I production through the TGF-β1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Cui

Zhang

Leng

et al. 2020

Cells

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“…Clinical observations support the view that inflammation is a prerequisite for the initiation of intestinal fibrosis, but neither inflammation alone nor the extent of inflammation seem to correlate well with the progression of fibrosis [ 54 , 55 ]. Once initiated, intestinal fibrogenesis may become an independent, self-perpetuating process, which would explain why the advent of highly effective anti-inflammatory biological agents seems not to have significantly reduced the incidence of fibrotic CD [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase 4 is protective and not fibrogenic in intestinal inflammation

et al. 2020

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Dysregulated redox signaling and oxidative injury are associated with inflammatory processes and fibrosis. H 2 O 2 generation by NOX4 has been suggested as a key driver in the development of fibrosis and a small molecule drug is under evaluation in clinical trials for idiopathic pulmonary fibrosis and primary biliary cholangitis. Fibrosis is a common complication in Crohn's disease (CD) leading to stricture formation in 35–40% of patients, who require surgical interventions in the absence of therapeutic options. Here we assess NOX4 expression in CD patients with inflammatory or stricturing disease and examine whether loss of NOX4 is beneficial in acute and fibrotic intestinal disease. NOX4 was upregulated in inflamed mucosal tissue of CD and ulcerative colitis (UC) patients, in CD ileal strictures, and in mice with intestinal inflammation. Nox4 deficiency in mice promoted pathogen colonization and exacerbated tissue injury in acute bacterial and chemical colitis. In contrast, in two chronic injury models aberrant tissue remodeling and fibrosis-related gene expression did not differ substantially between Nox4 −/− mice and wildtype mice, suggesting that Nox4 is dispensable in TGF-β1-driven intestinal fibrogenesis. While animal models do not recapitulate all the hallmarks of CD fibrosis, the tissue-protective role of Nox4 warrants a cautious approach to pharmacological inhibitors.

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“…In this review, we will not focus on fibrosis, since excellent reviews have already been published on the role of fibroblasts in fibrosis. 24–26 It is, however, an oversimplification to see fibroblasts only as passive matrix-depositing cells, thereby providing epithelial support and tissue structure. Recent literature shows that fibroblasts also play an important role in maintaining tissue homeostasis by their interaction with both epithelial and immune cells.…”

Section: Stromal Cells In Intestinal Homeostasismentioning

confidence: 99%

Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease

Barnhoorn

Hakuno

Bruckner

et al. 2020

Journal of Crohn's and Colitis

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Up till now, research on inflammatory bowel disease [IBD] has mainly been focused on the immune cells present in the gastrointestinal tract. However, recent insights indicate that stromal cells also play an important and significant role in IBD pathogenesis. Stromal cells in the intestines regulate both intestinal epithelial and immune cell homeostasis. Different subsets of stromal cells have been found to play a role in other inflammatory diseases [e.g. rheumatoid arthritis], and these various stromal subsets now appear to carry out also specific functions in the inflamed gut in IBD. Novel potential therapies for IBD utilize, as well as target, these pathogenic stromal cells. Injection of mesenchymal stromal cells [MSCs] into fistula tracts of Crohn’s disease patients is already approved and used in clinical settings. In this review we discuss the current knowledge of the role of stromal cells in IBD pathogenesis. We further outline recent attempts to modify the stromal compartment in IBD with agents that target or replace the pathogenic stroma.

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Intestinal fibrosis

Cited by 52 publications

References 70 publications

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

NADPH oxidase 4 is protective and not fibrogenic in intestinal inflammation

Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease

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