{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:57:55Z","timestamp":1790776675976,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The study aimed to investigate the role of Long non-coding RNA (LncRNA) H19 in the pathogenesis of Diarrhea Irritable Bowel Syndrome (IBS-D), and further to the regulatory effect of LncRNA H19 on AQP1, 3 in the intestinal mucosa of IBS-D patients, so as to seek a new way to elucidate the mechanism of IBS in clinic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The levels of LncRNA H19, AQP1, and AQP3 were detected in colonic tissues of IBS-D patients, compared with that in healthy controls. Through RNA gene interference and activation methods, small activating RNA (saRNA) and small interfering (siRNA) were transfered into Caco-2 cells <jats:italic>in vitro<\/jats:italic> experiment, and sub-group for two control group, siH19 empty vector group, siH19 interference group, overexpression H19 vector group, and overexpression H19 empty vector group. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were applied to evaluate the expression levels of LncRNA H19 and the amount of AQP1 and AQP3 protein expression, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with healthy volunteers, the levels of LncRNA H19, AQP1, and AQP3 in the colonic mucosa of IBS-D patients were significantly decreased (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). The results <jats:italic>in vitro<\/jats:italic> transfection experiment revealed that the level of LncRNA H19 in the siH19 interference group was significantly declined (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), while there was a remarkable increase in the overexpression H19 vector group (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), compared with the corresponding control groups. The expression of AQP1 and AQP3 in Caco-2 cells was of positive correlation with the level of LncRNA H19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>That the down-regulation of LncRNA H19 resulted in the expression changes of AQP1 and AQP3 may play an important role in the occurrence and development of IBS-D.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2020.602076","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T09:11:53Z","timestamp":1610529113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["LncRNA H19 as a Competing Endogenous RNA to Regulate AQP Expression in the Intestinal Barrier of IBS-D Patients"],"prefix":"10.3389","volume":"11","author":[{"given":"Guanqun","family":"Chao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/351153a0","article-title":"Parental imprinting of the mouse H19 gene.","volume":"351","author":"Bartolomei","year":"1991","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000019","article-title":"Aquaporin Expression in Colonic Mucosal Biopsies From Irritable Bowel Syndrome With Diarrhea.","volume":"10","author":"Camilleri","year":"2019","journal-title":"Clin. Transl. Gastroenterol."},{"key":"B3","first-page":"4117","article-title":"Aquaporins 1, 3 and 8 expression and cytokines in irritable bowel syndrome rats\u2019colon via cAMP-PKA pathway.","volume":"11","author":"Chao","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2582","DOI":"10.1097\/mib.0000000000000932","article-title":"Effect of Long Noncoding RNA H19 Overexpression on Intestinal Barrier Function and Its Potential Role in the Pathogenesis of Ulcerative Colitis.","volume":"22","author":"Chen","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1053\/j.gastro.2016.03.035","article-title":"Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction.","volume":"150","author":"Drossman","year":"2016","journal-title":"Gastroenterology."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/j.biopha.2018.06.007","article-title":"LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis.","volume":"105","author":"Fang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s40291-018-0380-6","article-title":"MicroRNAs and Long Non-coding RNAs in Genetic Diseases.","volume":"23","author":"Finotti","year":"2019","journal-title":"Mol. Diagn. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1053\/j.gastro.2018.03.058","article-title":"In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration.","volume":"155","author":"Geng","year":"2018","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1053\/j.gastro.2017.05.037","article-title":"Irritable Bowel Syndrome-Type Symptoms Are Associated With Psychological Comorbidity, Reduced Quality of Life, and Health Care Use in Patients With Inflammatory Bowel Disease.","volume":"153","author":"Gracie","year":"2017","journal-title":"Gastroenterology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1159\/000486059","article-title":"MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1.","volume":"44","author":"Hou","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109206","article-title":"Berberine improves intestinal epithelial tight junctions by upregulating A20 expression in IBS-D mice.","volume":"118","author":"Hou","year":"2019","journal-title":"Biomed. Pharmacother"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153782","article-title":"Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model.","volume":"20","author":"Ikarashi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1093\/nar\/28.5.1221","article-title":"Evidence for evolutionarily conserved secondary structure in the H19 tumor suppressor RNA.","volume":"28","author":"Juan","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.parepi.2019.e00112","article-title":"Blastocystis ST-1 is associated with Irritable Bowel Syndrome-diarrhoea (IBS-D) in Indonesian adolescences.","volume":"6","author":"Kesuma","year":"2019","journal-title":"Parasite Epidemiol. Control"},{"key":"B15","first-page":"3438","article-title":"Tumor-released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non-small cell lung cancer.","volume":"40","author":"Lei","year":"2018","journal-title":"Oncol Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/375034a0","article-title":"Disruption of imprinting caused by deletion of the H19 gene region in mice.","volume":"375","author":"Leighton","year":"1995","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5878","DOI":"10.1111\/jcmm.15262","article-title":"Epidermal growth factor regulation by autophagy-mediated lncRNA H19 in murine intestinal tract after severe burn.","volume":"24","author":"Li","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"B18","doi-asserted-by":"crossref","first-page":"C126","DOI":"10.1152\/ajpcell.2001.280.1.C126","article-title":"Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels.","volume":"280","author":"Ma","year":"2001","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7275","DOI":"10.1073\/pnas.90.15.7275","article-title":"Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia.","volume":"90","author":"Nielsen","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B20","first-page":"322","article-title":"LncRNA H19 promotes atherosclerosis by regulating MAPK and NF-kB signaling pathway.","volume":"21","author":"Pan","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1159\/000486155","article-title":"Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo.","volume":"44","author":"Pan","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1002\/1873-3468.12171","article-title":"LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier.","volume":"590","author":"Su","year":"2016","journal-title":"FEBS Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00125-018-4797-6","article-title":"lncRNA H19 prevents endothelial-mesenchymal transition in diabetic retinopathy.","volume":"62","author":"Thomas","year":"2019","journal-title":"Diabetologia"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3585","DOI":"10.18632\/aging.101999","article-title":"Blocking lncRNA H19-miR-19a-Id2 axis attenuates hypoxia\/ischemia induced neuronal injury.","volume":"11","author":"Xiao","year":"2019","journal-title":"Aging"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1016\/j.febslet.2011.08.045","article-title":"Knockdown of aquaporin 3 is involved in intestinal barrier integrity impairment.","volume":"585","author":"Zhang","year":"2011","journal-title":"FEBS Lett."},{"key":"B26","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3109\/10520295.2016.1144079","article-title":"Expression, localization and possible functions of aquaporins 3 and 8 in rat digestive system.","volume":"91","author":"Zhao","year":"2016","journal-title":"Biotech. Histochem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.febslet.2014.01.022","article-title":"MiR-874 promotes intestinal barrier dysfunction through targeting AQP3 following intestinal ischemic injury.","volume":"588","author":"Zhi","year":"2014","journal-title":"FEBS Lett."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1128\/mcb.01030-15","article-title":"H19 Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR.","volume":"36","author":"Zou","year":"2016","journal-title":"Mol. Cell Biol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2020.602076\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T17:48:38Z","timestamp":1610560118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2020.602076\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,12]]},"references-count":28,"alternative-id":["10.3389\/fphys.2020.602076"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2020.602076","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,12]]},"article-number":"602076"}}