Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory Bowel Diseases

Rieder, Florian; Fiocchi, Claudio; Rogler, Gerhard

doi:10.1053/j.gastro.2016.09.047

Cited by 384 publications

(438 citation statements)

References 221 publications

(181 reference statements)

Supporting

Mentioning

427

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, IBD progression is associated with the development of a number of common complications. For example, inflammation associated with CD often leads to fibrosis 90 . Other complications such as anemia also are associated with IBD.…”

Section: Inflammatory Bowel Disease: the Involvement Of Barrier Dysfumentioning

confidence: 99%

“…Anti-TNF therapy can lead to immune-compromised states and is related to a higher risk of infectious disease as well as a higher risk of malignancy 93 . Moreover, complications such as fibrosis still can appear and represent major indication for surgical interventions owing to the lack of pharmacologic options 90 . This emphasizes the need for new therapeutic approaches that can prolong remission and control the development of complications.…”

Section: Inflammatory Bowel Disease: the Involvement Of Barrier Dysfumentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function

Manresa¹,

Taylor

2017

Cellular and Molecular Gastroenterology and Hepatology

View full text Add to dashboard Cite

Human health is dependent on the ability of the body to extract nutrients, fluids, and oxygen from the external environment while at the same time maintaining a state of internal sterility. Therefore, the cell layers that cover the surface areas of the body such as the lung, skin, and gastrointestinal mucosa provide vital semipermeable barriers that allow the transport of essential nutrients, fluid, and waste products, while at the same time keeping the internal compartments free of microbial organisms. These epithelial surfaces are highly specialized and differ in their anatomic structure depending on their location to provide appropriate and effective site-specific barrier function. Given this important role, it is not surprising that significant disease often is associated with alterations in epithelial barrier function. Examples of such diseases include inflammatory bowel disease, chronic obstructive pulmonary disease, and atopic dermatitis. These chronic inflammatory disorders often are characterized by diminished tissue oxygen levels (hypoxia). Hypoxia triggers an adaptive transcriptional response governed by hypoxia-inducible factors (HIFs), which are repressed by a family of oxygen-sensing HIF hydroxylases. Here, we review recent evidence suggesting that pharmacologic hydroxylase inhibition may be of therapeutic benefit in inflammatory bowel disease through the promotion of intestinal epithelial barrier function through both HIF-dependent and HIF-independent mechanisms.

show abstract

Section: Inflammatory Bowel Disease: the Involvement Of Barrier Dysfumentioning

confidence: 99%

Section: Inflammatory Bowel Disease: the Involvement Of Barrier Dysfumentioning

confidence: 99%

Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function

Manresa¹,

Taylor

2017

Cellular and Molecular Gastroenterology and Hepatology

View full text Add to dashboard Cite

show abstract

“…CD-associated strictures are frequently unresponsive to any of the current anti-inflammatory drugs for CD and require alternative therapeutic approaches like endoscopic balloon dilation (3•), strictureplasty or bowel resection, and often recur after resection (2, 4, 5). Clinically, the CD fibrostenotic stricture needs to be distinguished from inflammation-related bowel wall thickening which may respond to anti-inflammatory therapy; the two often coexist, and their distinction is difficult since intestinal fibrosis follows the distribution and location of inflammation (6).…”

Section: Morphology and Mechanisms Of Intestinal Fibrosismentioning

confidence: 99%

“…Of these enteropathies, IBD is the main cause of intestinal fibrosis since this disease is characterized by a persistent immuno-mediated intestinal inflammation (1, 2). It becomes clinically apparent in >30% of patients with Crohn’s disease (CD) and in about 5% with ulcerative colitis (UC).…”

Section: Introductionmentioning

confidence: 99%

Intestinal fibrosis

Latella

Rieder

2017

Current Opinion in Gastroenterology

Self Cite

View full text Add to dashboard Cite

Purpose of the review Intestinal fibrosis is a common complication of several enteropathies with inflammatory bowel disease being the major cause. Intestinal fibrosis affects both ulcerative colitis and Crohn’s disease, and no specific anti-fibrotic therapy exists. This review highlights recent developments in this area. Recent findings The pathophysiology of intestinal stricture formation includes inflammation dependent and independent mechanisms. A better understanding of the mechanisms of intestinal fibrogenesis and the availability of compounds for other, non intestinal fibrotic diseases bring clincial trials in stricturing Crohn’s disease within reach. Summary Improved understanding of its mechanisms and ongoing development of clincial trial endpoints for intestinal fibrosis will allow the testing of novel anti-fibrotic compounds in inflammatory bowel disease.

show abstract

“…As known, intestinal fibrosis is a consequence of local chronic inflammation and is characterized by excessive ECM protein deposition [22]. The transforming growth factor-β1 (TGF-β1) isoform was considered to be closely involved in fibrosis and ECM synthesis.…”

Section: Introductionmentioning

confidence: 99%

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

et al. 2019

View full text Add to dashboard Cite

Background: Intestinal fibrosis is the major complication of Crohn’s disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. Methods: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-β1 (TGF-β1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-β/Smad pathway. Results: The results showed that the concentration of CA was 12.5, 25, 50 μmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-β/Smad signaling pathway. Conclusion: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-β/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-β1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-β/Smad pathway.

show abstract

Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory Bowel Diseases

Cited by 384 publications

References 221 publications

Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function

Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function

Intestinal fibrosis

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Contact Info

Product

Resources

About