ArticlePloS one2015
All-Trans Retinoic Acid Induces TGF-β2 in Intestinal Epithelial Cells via RhoA- and p38α MAPK-Mediated Activation of the Transcription Factor ATF2.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Putative molecular targets for vitamin A in neutralizing oxidative stress in acute and chronic pancreatitis - a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2023Pooled it
- Vitamins as modulators of neonatal intestinal injury.Frontiers in nutrition · 2026Review
- All-trans retinoic acid modulates proliferation and apoptosis of secondary hair follicle-dermal papilla cells in cashmere goats via the TGF-Frontiers in veterinary science · 2026Article
- MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.Molecular oncology · 2024Article
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
- Shaping infant development from the inside out: Bioactive factors in human milk.Seminars in perinatology · 2023Review
- Role of macrophages in fetal development and perinatal disorders.Pediatric research · 2021Review
- TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation.Cancer science · 2020Article
- Adaptation of extracellular matrix to massive small bowel resection in mice.Journal of pediatric surgery · 2020Article
- Review
- Effects of all-trans retinoic acid on the in vitro maturation of camel (Camelus dromedarius) cumulus-oocyte complexes.The Journal of reproduction and development · 2019Article
- Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid.Journal of lipid research · 2019Article
- Retinoic Acid, Leaky Gut, and Autoimmune Diseases.Nutrients · 2018Review
- SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression.Journal of experimental & clinical cancer research : CR · 2018Article
- Rho GTPase signaling promotes constitutive expression and release of TGF-β2 by human trabecular meshwork cells.Experimental eye research · 2016Article
- Levels and effectiveness of oral retinol supplementation in VLBW preterm infants.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveWe have shown previously that preterm infants are at risk of necrotizing enterocolitis (NEC), an inflammatory bowel necrosis typically seen in infants born prior to 32 weeks' gestation, because of the developmental deficiency of transforming growth factor (TGF)-β2 in the intestine. The present study was designed to investigate all-trans retinoic acid (atRA) as an inducer of TGF-β2 in intestinal epithelial cells (IECs) and to elucidate the involved signaling mechanisms.
methodsAtRA effects on intestinal epithelium were investigated using IEC6 cells. TGF-β2 expression was measured using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and Western blots. Signaling pathways were investigated using Western blots, transiently-transfected/transduced cells, kinase arrays, chromatin immunoprecipitation, and selective small molecule inhibitors.
resultsAtRA-treatment of IEC6 cells selectively increased TGF-β2 mRNA and protein expression in a time- and dose-dependent fashion, and increased the activity of the TGF-β2 promoter. AtRA effects were mediated via RhoA GTPase, Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1), p38α MAPK, and activating transcription factor (ATF)-2. AtRA increased phospho-ATF2 binding to the TGF-β2 promoter and increased histone H2B acetylation in the TGF-β2 nucleosome, which is typically associated with transcriptional activation.
conclusionsAtRA induces TGF-β2 expression in IECs via RhoA- and p38α MAPK-mediated activation of the transcription factor ATF2. Further studies are needed to investigate the role of atRA as a protective/therapeutic agent in gut mucosal inflammation.
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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.