Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn’s Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme

Chen, Wenqian; Lu, Cathy; Hirota, Christina L.; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong

doi:10.1093/ecco-jcc/jjw126

Cited by 127 publications

(144 citation statements)

References 41 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…Because chronic inflammation in IBD carries the certainty of repeated inflammatory episodes, the unknown factors that cause IBD may, in some individuals, converge to cause locally severe outcomes. These appear as intestinal strictures, where smooth muscle is the single largest contributor to histopathology (8). More broadly, the loss of contractile protein and decreased sensitivity to contractile agonists such as acetylcholine may contribute to the altered motility that characterizes the inflamed intestine.…”

Section: Discussionmentioning

confidence: 99%

“…In Crohn's disease, one of the types of human inflammatory bowel disease (IBD), intestinal strictures that cause obstructive symptoms are a frequent complication (44). The histopathology of both animal models and Crohn's strictures shows an excessive growth of ISMC (8,12,19,27), but there is no direct evidence for an alteration of the contractile phenotype. Since this might arise from protracted growth of ISMC and could be a major contributor to altered function, we examined sections of ileal Crohn's strictures for expression of contractile markers.…”

Section: Effect Of Proliferation or Chronic Inflammation On Phenotypementioning

confidence: 99%

“…Smooth muscle proliferation occurs in animal models of intestinal inflammation (3,17,26) and in Crohn's strictures (10), where increased collagen is a major contributor to increased ECM (21). Overall, the dominant pathophysiological feature of Crohn's strictures is increased representation of smooth muscle in the external muscle layers (8), suggesting that smooth muscle hyperplasia is a major driving force in stricture formation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic modification of intestinal smooth muscle cell phenotype during proliferation

Bonafiglia

Lourenssen

Hurlbut

et al. 2018

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Inflammation causes proliferation of intestinal smooth muscle cells (ISMC), which contributes to a thickened intestinal wall, and also to stricture formation in Crohn's disease. Proliferation of ISMC both in vitro and in vivo caused decreased expression of marker proteins, but the underlying cause is unclear. Since epigenetic change is important in other systems, we examined this in cell lines from rat colon at either low passage or after extended growth, using immunocytochemistry, immunoblotting and qPCR to evaluate phenotype. Exposure to the HDAC inhibitor trichostatin A or 5-azacytidine, a DNMT inhibitor, reversed the characteristic loss of phenotypic markers among high passage cell lines of ISMC. Expression of smooth muscle actin and SM-22 were markedly increased, as well as functional expression of the neurotrophin GDNF. Increased expression of muscarinic receptor-3 and MLCK was correlated with an upregulated response to cholinergic stimulation. In human ISMC (hISMC) lines from terminal ileum, phenotype was similarly affected by extended proliferation. However, hISMC from resected Crohn's strictures at low passage already displayed a significantly reduced contractile phenotype, compared with patient-matched intrinsic controls, and was associated with increased, patient-specific expression of DNMT1, HDAC2, and HDAC5. Therefore, protracted growth causes epigenetic alterations that account for an altered phenotype of ISMC. A similar process may promote stricture formation in Crohn's disease, where the potential for halting progression or even reversal of disease through control of phenotypic modulation may become a novel treatment option.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Proliferation or Chronic Inflammation On Phenotypementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic modification of intestinal smooth muscle cell phenotype during proliferation

Bonafiglia

Lourenssen

Hurlbut

et al. 2018

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…It affects any part of the gastrointestinal tract and results in narrowing of the lumen leading to strictures that frequrntly cause intestinal obstruction. It has recently been reported that the smooth muscle hyperplasia/hypertrophy contributes to the majority of the CD stricturing phenotype, whereas fibrosis may be less significant (8•). In this report the authors proposed a novel histological grading system that covers not only inflammation and fibrosis but the full spectrum of inflammatory bowel disease pathology.…”

Section: Morphology and Mechanisms Of Intestinal Fibrosismentioning

confidence: 99%

Intestinal fibrosis

Latella

Rieder

2017

Current Opinion in Gastroenterology

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

“…The thickened bowel wall consists of smooth muscle hypertrophy together with fibrosis, inflammation, and mucosal ulcers . De novo and anastomotic strictures may be associated with particular microbial “signatures.”…”

mentioning

confidence: 99%

Editorial: treating strictures in inflammatory bowel disease

Kamm

2018

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn’s Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme

Abstract: In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures.

Cited by 127 publications

References 41 publications

Epigenetic modification of intestinal smooth muscle cell phenotype during proliferation

Epigenetic modification of intestinal smooth muscle cell phenotype during proliferation

Intestinal fibrosis

Editorial: treating strictures in inflammatory bowel disease

Contact Info

Product

Resources

About