Mechano-Regulation of Gene Expression in the Gut: Implications in Pathophysiology and Therapeutic Approaches in Obstructive, Inflammatory, and Functional Bowel Disorders

Shi, Xuan–Zheng

doi:10.1016/b978-0-12-820472-6.00168-7

Cited by 2 publications

(2 citation statements)

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“…Obstructive bowel disorders (OBD) are characterized by lumen distention due to mechanical or functional bowel obstruction (BO) in the gut and present significant health challenges in adults and children ( Welch and Welch, 1990 ; Shi and Terry, 2022 ). Current investigations focus mainly on the local dysfunctions in the gut, i.e., dysmotility, abdominal pain, and altered secretion and absorption functions ( Roeland and von Gunten, 2009 ; Shi et al, 2011 ; Lin et al, 2017 ; Shi et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…Current investigations focus mainly on the local dysfunctions in the gut, i.e., dysmotility, abdominal pain, and altered secretion and absorption functions ( Roeland and von Gunten, 2009 ; Shi et al, 2011 ; Lin et al, 2017 ; Shi et al, 2018 ). However, bowel obstruction may lead to severe systemic responses, such as sepsis, septic shock, immune dysfunction, recurrent inflammation, and infections ( Welch and Welch, 1990 ; Catena et al, 2019 ; Shi and Terry, 2022 ). In fact, most of the BO-related deaths (236,000 annually in the world) are due to systemic responses ( Cappell and Batke, 2008 ; Catena et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of lymphoid depletion in bowel obstruction

et al. 2022

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Background and aims: Bowel obstruction (BO) causes not only gastrointestinal dysfunctions but also systemic responses such as sepsis, infections, and immune impairments. The mechanisms involved are not well understood. In this study, we tested the hypothesis that BO leads to lymphoid depletion in primary and peripheral lymphoid organs, which may contribute to systemic responses. We also sought to uncover mechanisms of lymphoid depletion in BO.Methods: Partial colon obstruction was induced with a band in the distal colon of Sprague-Dawley rats, and wild-type and osteopontin knockout (OPN−/−) mice. Obstruction was maintained for 7 days in rats and 4 days in mice. Thymus, bone marrow, spleen, and mesenteric lymph node (MLN) were taken for flow cytometry analysis.Results: The weight of thymus, spleen, and MLN was significantly decreased in BO rats, compared to sham. B and T lymphopoiesis in the bone marrow and thymus was suppressed, and numbers of lymphocytes, CD4+, and CD8+ T cells in the spleen and MLN were all decreased in BO. Depletion of gut microbiota blocked BO-associated lymphopenia in the MLN. Corticosterone antagonism partially attenuated BO-associated reduction of lymphocytes in the thymus and bone marrow. Plasma OPN levels and OPN expression in the distended colon were increased in BO. Deletion of the OPN gene did not affect splenic lymphopenia, but attenuated suppression of lymphopoiesis in the bone marrow and thymus in BO.Conclusions: BO suppresses lymphocyte generation and maintenance in lymphoid organs. Mechanical distention-induced OPN, corticosterone, and gut microbiota are involved in the immune phenotype in BO.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of lymphoid depletion in bowel obstruction

et al. 2022

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Mechanical stress-induced connective tissue growth factor plays a critical role in intestinal fibrosis in Crohn’s-like colitis

Lin,

Zhang,

Geesala

et al. 2024

American Journal of Physiology-Gastrointestinal and Liver Physi

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Crohn's disease (CD) is an inflammatory bowel disease characterized by transmural inflammation and intestinal fibrosis. Mechanisms of fibrosis in CD are not well understood. Transmural inflammation is associated with inflammatory cell infiltration, stenosis, and distention, which present mechanical stress (MS) to the bowel wall. We hypothesize that MS induces gene expression of pro-fibrotic mediators such as connective tissue growth factor (CTGF), which may contribute to fibrosis in CD. A rodent model of CD was induced by intracolonic instillation of TNBS to the distal colon. TNBS instillation induced a localized transmural inflammation (site I), with a distended colon segment (site P) proximal to site I. We detected significant fibrosis and collagen content not only in site I, but also in site P in CD rats by day 7. CTGF expression increased significantly in sites P and I, but not in the segment distal to the inflammation site. Increased CTGF expression was detected mainly in the smooth muscle cells (SMC). When rats were fed exclusively with clear liquid diet to prevent mechanical distention in colitis, expression of CTGF in sites P and I was blocked. Direct stretch led to robust expression of CTGF in colonic SMC. Treatment of CD rats with anti-CTGF antibody FG-3149 reduced fibrosis and collagen content in both sites P and I and exhibited consistent trends towards normalizing expression of collagen mRNAs. In conclusion, our studies suggest that mechanical stress, by up-regulating pro-fibrotic mediators i.e. CTGF, may play a critical role in fibrosis in CD.

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Mechano-Regulation of Gene Expression in the Gut: Implications in Pathophysiology and Therapeutic Approaches in Obstructive, Inflammatory, and Functional Bowel Disorders

Cited by 2 publications

References 186 publications

Mechanisms of lymphoid depletion in bowel obstruction

Mechanisms of lymphoid depletion in bowel obstruction

Mechanical stress-induced connective tissue growth factor plays a critical role in intestinal fibrosis in Crohn’s-like colitis

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