ArticleCell death & disease2018
DNA methylation, through DNMT1, has an essential role in the development of gastrointestinal smooth muscle cells and disease.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Folic acid improves intestinal function in grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Vitamin A deficiency triggers colonic methylation potentially impairing colonic neuron via downregulation SGK1/FOXO pathway.Pediatric discovery · 2024Article
- DNA methylation in necrotizing enterocolitis.Expert reviews in molecular medicine · 2024Review
- Article
- PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1.International journal of molecular sciences · 2023Article
- Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis.Bioactive materials · 2022Article
- DNA methyltransferase 1 (DNMT1) suppresses mitophagy and aggravates heart failure via the microRNA-152-3p/ETS1/RhoH axis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Article
- Dnmt1 is required for the development of auditory organs via cell cycle arrest and Fgf signalling.Cell proliferation · 2022Article
- Epigenetic Regulation of Intestinal Stem Cells and Disease: A Balancing Act of DNA and Histone Methylation.Gastroenterology · 2021Review
- Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy.Clinical epigenetics · 2021Review
- Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Epigenetic factors Dnmt1 and Uhrf1 coordinate intestinal development.Developmental biology · 2019Article
- MeCP2 inhibits cell functionality through FoxO3a and autophagy in endothelial progenitor cells.Aging · 2019Article
- Role of DNA Methylation in the Development and Differentiation of Intestinal Epithelial Cells and Smooth Muscle Cells.Journal of neurogastroenterology and motility · 2019Review
- DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation.Journal of the American Society of Nephrology : JASN · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMCs) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMCs are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency. Dnmt1-KO pups are born smaller than their wild-type littermates, have shortened GI tracts, and lose peristaltic movement due to loss of the tunica muscularis in their intestine, causing massive intestinal dilation, and death around postnatal day 21. Within smooth muscle tissue, significant CpG hypomethylation occurs across the genome at promoters, introns, and exons. Additionally, there is a marked loss of differentiated SMC markers (Srf, Myh11, miR-133, miR-143/145), an increase in pro-apoptotic markers (Nr4a1, Gadd45g), loss of cellular connectivity, and an accumulation of coated vesicles within SMC. Interestingly, we observed consistent abnormal expression patterns of enzymes involved in DNA methylation between both Dnmt1-KO mice and diseased human GI tissue. These data demonstrate that DNA hypomethylation in embryonic SMC, via congenital Dnmt1 deficiency, contributes to massive dysregulation of gene expression and is lethal to GI-SMC. These results suggest that Dnmt1 has a necessary role in the embryonic, primary development process of SMC with consistent patterns being found in human GI diseased tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.