Role of DNA Methylation in the Development and Differentiation of Intestinal Epithelial Cells and Smooth Muscle Cells

A hallmark of ulcerative colitis is the chronic colonic inflammation, which is the result of a dysregulated intestinal mucosal immune response. Epithelial barrier disruption which allows the entry of microorganisms eventually leads to more aggressive inflammation and potentially the removal of the colon. We have previously shown that the T helper- (Th-) type 2 cytokines, Interleukin- (IL-) 4 and IL-13, mediate CD4+ T cell- or B cell-driven inflammation in the oxazolone-induced mouse model of ulcerative colitis. In contrast, mice deficient in the shared receptor of IL-4 and IL-13, IL-4 receptor-alpha (IL-4Rα), on all cells develop an exacerbated disease phenotype. This suggests that a regulatory role of IL-4Rα is required to protect against severe colitis. However, the cell populations responsible for regulating the severity of disease onset through IL-4Rα in colitis are yet to be identified. By deleting IL-4Rα on specific cell subsets shown to play a role in mediating colitis, we determined their role in a loss of function approach. Our data demonstrated that the loss of IL-4Rα signalling on intestinal epithelial cells, smooth muscle cells, and macrophages/neutrophils had no effect on alleviating the pathology associated with colitis. These results suggest that IL-4/IL-13 signalling through IL-4Rα on nonhematopoietic intestinal epithelial or smooth muscle cells and hematopoietic macrophage/neutrophils has a redundant role in driving acute oxazolone colitis.

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Direct effect of croton oil on intestinal epithelial cells and colonic smooth muscle cells

World Journal of Gastroenterology ◽

10.3748/wjg.v8.i1.103 ◽

2002 ◽

Vol 8 (1) ◽

pp. 103 ◽

Cited By ~ 20

Author(s):

Xin Wang

Keyword(s):

Smooth Muscle ◽

Epithelial Cells ◽

Smooth Muscle Cells ◽

Direct Effect ◽

Intestinal Epithelial Cells ◽

Muscle Cells ◽

Intestinal Epithelial ◽

Croton Oil

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Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations

10.21203/rs.3.rs-1041773/v1 ◽

2021 ◽

Author(s):

Ryo Maekawa ◽

Shun Sato ◽

Tetsuro Tamehisa ◽

Takahiro Sakai ◽

Takuya Kajimura ◽

...

Keyword(s):

Dna Methylation ◽

Extracellular Matrix ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Blood Vessels ◽

Uterine Fibroids ◽

Muscle Cells ◽

Histological Features ◽

Dna Methylome

Abstract Background: Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological features between MED12m-positive and -negative UFs. Methods: DNA methylomes and transcriptomes were obtained from MED12m-positive and -negative UFs and myometrium, and hierarchically clustered. Differentially expressed genes in comparison with the myometrium and co-expressed genes detected by weighted gene co-expression network analysis were subjected to gene ontology enrichment analyses. The amounts of collagen fibers and the number of blood vessels and smooth muscle cells were histologically evaluated. Results: Hierarchical clustering based on DNA methylation clearly separated the myometrium, MED12m-positive, and MED12m-negative UFs. MED12m-positive UFs had the increased activities of extracellular matrix formation, whereas MED12m-negative UFs had the increased angiogenic activities and smooth muscle cell proliferation. Conclusion: The MED12m-positive and -negative UFs had different DNA methylation, gene expression, and histological features. The MED12m-positive UFs form the tumor with a rich extracellular matrix and poor blood vessels and smooth muscle cells compared to the MED12m-negative UFs, suggesting MED12 mutations affect the tissue composition of UFs.

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997 – Dietary and Phenotypic Insights Into the Role of Dna Methylation in the Regulation, Development and Growth of Embryonic and Adult Gastrointestinal Smooth Muscle Cells

Gastroenterology ◽

10.1016/s0016-5085(19)37329-9 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-212

Author(s):

Brian Jorgensen ◽

Seeun Ha ◽

Moon Young Lee ◽

Robyn Berent ◽

Paul Park ◽

...

Keyword(s):

Dna Methylation ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Gastrointestinal Smooth Muscle ◽

Regulation Development

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Paracrine regulation of the renal microcirculation

Physiological Reviews ◽

10.1152/physrev.1996.76.2.425 ◽

1996 ◽

Vol 76 (2) ◽

pp. 425-536 ◽

Cited By ~ 558

Author(s):

L. G. Navar ◽

E. W. Inscho ◽

S. A. Majid ◽

J. D. Imig ◽

L. M. Harrison-Bernard ◽

...

Keyword(s):

Smooth Muscle ◽

Epithelial Cells ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Microvascular Function ◽

Paracrine Regulation ◽

Renal Vascular

There has been an explosive growth of interest in the multiple interacting paracrine systems that influence renal microvascular function. This review first discusses the membrane activation mechanisms for renal vascular control. Evidence is provided that there are differential activating mechanisms regulating pre- and postglomerular arteriolar vascular smooth muscle cells. The next section deals with the critical role of the endothelium in the control of renal vascular function and covers the recent findings related to the role of nitric oxide and other endothelial-derived factors. This section is followed by an analysis of the roles of vasoactive paracrine systems that have their origin from adjoining tubular structures. The interplay of signals between the epithelial cells and the vascular network to provide feedback regulation of renal hemodynamics is developed. Because of their well-recognized contributions to the regulation of renal microvascular function, three major paracrine systems are discussed in separate sections. Recent findings related to the role of intrarenally formed angiotensin II and the prominence of the AT1 receptors are described. The possible contribution of purinergic compounds is then discussed. Recognition of the emerging role of extracellular ATP operating via P2 receptors as well as the more recognized functions of the P1 receptors provides fertile ground for further studies. In the next section, the family of vasoactive arachidonic acid metabolites is described. Possibilities for a myriad of interacting functions operating both directly on vascular smooth muscle cells and indirectly via influences on endothelial and epithelial cells are discussed. Particular attention is given to the more recent developments related to hemodynamic actions of the cytochrome P-450 metabolites. The final section discusses unique mechanisms that may be responsible for differential regulation of medullary blood flow by locally formed paracrine agents. Several sections provide perspectives on the complex interactions among the multiple mechanisms responsible for paracrine regulation of the renal microcirculation. This plurality of regulatory interactions highlights the need for experimental strategies that include integrative approaches that allow manifestation of indirect as well as direct influences of these paracrine systems on renal microvascular function.

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Cellular Distribution of the Angiogenic Factor Heparin Affin Regulatory Peptide (HARP) mRNA and Protein in the Human Mammary Gland

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215549704500907 ◽

1997 ◽

Vol 45 (9) ◽

pp. 1239-1245 ◽

Cited By ~ 12

Author(s):

Dominique Ledoux ◽

Daniele Caruelle ◽

Jean-Christophe Sabourin ◽

Jianfeng Liu ◽

Michel Crepin ◽

...

Keyword(s):

Smooth Muscle ◽

Mammary Gland ◽

Epithelial Cells ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Angiogenic Factor ◽

Cellular Distribution ◽

Regulatory Peptide ◽

Human Mammary Gland

The heparin affin regulatory peptide (HARP) growth factor, also known as pleiotrophin, is a developmentally regulated protein that displays biological functions during cell growth and differentiation. To study the physiological role of this protein, we investigated the cellular distribution of HARP mRNA and protein in the resting human mammary gland. In situ hybridization histochemistry revealed that HARP mRNA was localized in alveolar myoepithelial cells, whereas alveolar epithelial cells were negative. In the stroma, HARP mRNA was localized in endothelial cells and smooth muscle cells of blood vessels. Interestingly, HARP protein and mRNA were not always co-localized. HARP protein immunocytochemistry staining was observed in an area including both alveolar myoepithelial and epithelial cells, although epithelial cells do not express HARP transcript. In contrast, the distribution of HARP protein is parallel to that of HARP mRNA in endothelial and vascular smooth muscle cells. In the light of these results, the putative role of HARP in controlling the proliferation and/or differentiation of the different mammary cell types is proposed and discussed.

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