{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:09:20Z","timestamp":1783163360019,"version":"3.54.6"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"12","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971061"],"award-info":[{"award-number":["31971061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903087"],"award-info":[{"award-number":["81903087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taishan Pandeng Scholar Program of Shandong Province","award":["tspd20210321"],"award-info":[{"award-number":["tspd20210321"]}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12,5]]},"abstract":"<jats:p>Lethal intestinal tissue toxicity is a common side effect and a dose-limiting factor in chemoradiotherapy. Chemoradiotherapy can trigger DNA damage and induce P53-dependent apoptosis in LGR5+ intestinal stem cells (ISCs). Gamma-aminobutyric acid (GABA) and its A receptors (GABAAR) are present in the gastrointestinal tract. However, the functioning of the GABAergic system in ISCs is poorly defined. We found that GABAAR \u03b11 (GABRA1) levels increased in the murine intestine after chemoradiotherapy. GABRA1 depletion in LGR5+ ISCs protected the intestine from chemoradiotherapy-induced P53-dependent apoptosis and prolonged animal survival. The administration of bicuculline, a GABAAR antagonist, prevented chemoradiotherapy-induced ISC loss and intestinal damage without reducing the chemoradiosensitivity of tumors. Mechanistically, it was associated with the reduction of reactive oxygen species\u2013induced DNA damage via the L-type voltage\u2013dependent Ca2+ channels. Notably, flumazenil, a GABAAR antagonist approved by the U.S. Food and Drug Administration, rescued human colonic organoids from chemoradiotherapy-induced toxicity. Therefore, flumazenil may be a promising drug for reducing the gastrointestinal side effects of chemoradiotherapy.<\/jats:p>","DOI":"10.1084\/jem.20220541","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T14:17:10Z","timestamp":1663683430000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of GABAA receptors in intestinal stem cells prevents chemoradiotherapy-induced intestinal toxicity"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-7429","authenticated-orcid":true,"given":"Cuiyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-400X","authenticated-orcid":true,"given":"Yuping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-3076","authenticated-orcid":true,"given":"Junjie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-5171","authenticated-orcid":true,"given":"Nannan","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-2316","authenticated-orcid":true,"given":"Haining","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5898-1460","authenticated-orcid":true,"given":"Wenyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9768-0695","authenticated-orcid":true,"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, State Key laboratory of Biotherapy and cancer center, West China Hospital, Sichuan University, Chengdu, Sichuan, China 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1955-5802","authenticated-orcid":true,"given":"Kun","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-2048","authenticated-orcid":true,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Medical Research Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8405-832X","authenticated-orcid":true,"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1269-1887","authenticated-orcid":true,"given":"Huili","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Systems Biomedicine and Research Center of Stem Cell and Regenerative Medicine, Shandong University Cheeloo Medical College, School of Basic Medical Sciences, Jinan, China 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7370-703X","authenticated-orcid":true,"given":"Jingxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-4512","authenticated-orcid":true,"given":"Dawei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 1"},{"name":"Laboratory of Medical Chemistry, GIGA-Stem Cells, Faculty of Medicine, University of Li\u00e8ge, CHU, Sart-Tilman, Li\u00e8ge, Belgium 11"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"2022092020043652600_bib1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/s13287-020-01887-1","article-title":"Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome","volume":"11","author":"Accarie","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"2022092020043652600_bib2","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/nature06488","article-title":"Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation","volume":"451","author":"Andang","year":"2008","journal-title":"Nature"},{"key":"2022092020043652600_bib3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1667\/RR14272.1","article-title":"GI consequences of cancer treatment: A clinical perspective","volume":"185","author":"Andreyev","year":"2016","journal-title":"Radiat. Res."},{"key":"2022092020043652600_bib4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.phrs.2014.12.001","article-title":"GABA and GABA receptors in the gastrointestinal tract: From motility to inflammation","volume":"93","author":"Auteri","year":"2015","journal-title":"Pharmacol. Res."},{"key":"2022092020043652600_bib5","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nature01368","article-title":"DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation","volume":"421","author":"Bakkenist","year":"2003","journal-title":"Nature"},{"key":"2022092020043652600_bib6","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.stem.2012.09.009","article-title":"Identifying the stem cell of the intestinal crypt: Strategies and pitfalls","volume":"11","author":"Barker","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2022092020043652600_bib7","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1093\/occmed\/kql011","article-title":"Medical management of radiation injuries: Current approaches","volume":"56","author":"Berger","year":"2006","journal-title":"Occup. Med."},{"key":"2022092020043652600_bib8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jneuroim.2008.08.017","article-title":"GABA, a natural immunomodulator of T lymphocytes","volume":"205","author":"Bjurst\u00f6m","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"2022092020043652600_bib9","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.2165\/00003495-199142060-00010","article-title":"Flumazenil: A reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist","volume":"42","author":"Brogden","year":"1991","journal-title":"Drugs"},{"key":"2022092020043652600_bib10","doi-asserted-by":"publisher","first-page":"4529","DOI":"10.1038\/onc.2012.467","article-title":"5-Fluorouracil signaling through a calcium-calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells","volume":"32","author":"Can","year":"2013","journal-title":"Oncogene"},{"key":"2022092020043652600_bib11","doi-asserted-by":"publisher","first-page":"3991","DOI":"10.1111\/bph.15149","article-title":"Metformin mitigates gastrointestinal radiotoxicity and radiosensitises P53 mutation colorectal tumours via optimising autophagy","volume":"177","author":"Chen","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"2022092020043652600_bib12","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling development and disease with organoids","volume":"165","author":"Clevers","year":"2016","journal-title":"Cell"},{"key":"2022092020043652600_bib13","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1016\/j.stemcr.2021.08.003","article-title":"Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells","volume":"16","author":"Vila Cuenca","year":"2021","journal-title":"Stem Cell Rep."},{"key":"2022092020043652600_bib14","doi-asserted-by":"publisher","first-page":"319","DOI":"10.3322\/canjclin.55.5.319","article-title":"Use of antioxidants during chemotherapy and radiotherapy should be avoided","volume":"55","author":"D\u2019Andrea","year":"2005","journal-title":"CA Cancer J. Clin."},{"key":"2022092020043652600_bib15","doi-asserted-by":"publisher","first-page":"111529","DOI":"10.1016\/j.fct.2020.111529","article-title":"Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS\/JNK mediated apoptotic pathway in human colorectal cancer cell","volume":"143","author":"Dey","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"2022092020043652600_bib16","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/0016-5085(88)90512-4","article-title":"Prospects for management of gastrointestinal injury associated with the acute radiation syndrome","volume":"95","author":"Dubois","year":"1988","journal-title":"Gastroenterology"},{"key":"2022092020043652600_bib17","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1182\/blood.2019004415","article-title":"The neurotransmitter receptor Gabbr1 regulates proliferation and function of hematopoietic stem and progenitor cells","volume":"137","author":"Shao","year":"2021","journal-title":"Blood"},{"key":"2022092020043652600_bib18","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/S1470-2045(17)30086-4","article-title":"Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (stockholm III): A multicentre, randomised, non-blinded, phase 3, non-inferiority trial","volume":"18","author":"Erlandsson","year":"2017","journal-title":"Lancet Oncol."},{"key":"2022092020043652600_bib19","doi-asserted-by":"publisher","first-page":"G733","DOI":"10.1152\/ajpgi.2000.279.4.G733","article-title":"Identification of gamma-aminobutyric acid receptor subunit types in human and rat liver","volume":"279","author":"Erlitzki","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2022092020043652600_bib20","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1038\/nprot.2015.088","article-title":"Efficient genetic engineering of human intestinal organoids using electroporation","volume":"10","author":"Fujii","year":"2015","journal-title":"Nat. Protoc."},{"key":"2022092020043652600_bib21","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nature15382","article-title":"Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer","volume":"526","author":"Gregorieff","year":"2015","journal-title":"Nature"},{"key":"2022092020043652600_bib22","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1172\/JCI43794","article-title":"Radioprotection: Smart games with death","volume":"120","author":"Gudkov","year":"2010","journal-title":"J. Clin. Invest."},{"key":"2022092020043652600_bib23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.dnarep.2015.12.009","article-title":"ATM kinase: Much more than a DNA damage responsive protein","volume":"39","author":"Guleria","year":"2016","journal-title":"DNA Repair"},{"key":"2022092020043652600_bib24","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.bbrc.2018.03.078","article-title":"Intrinsic attenuation of post-irradiation calcium and ER stress imparts significant radioprotection to lepidopteran insect cells","volume":"498","author":"Guleria","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2022092020043652600_bib25","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nrgastro.2014.46","article-title":"Radiation enteropathy-pathogenesis, treatment and prevention","volume":"11","author":"Hauer-Jensen","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2022092020043652600_bib26","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.mrrev.2016.07.006","article-title":"The role of gene mutations and gene products in intestinal tissue reactions from ionising radiation","volume":"770","author":"Hendry","year":"2016","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"2022092020043652600_bib27","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00726-011-1193-7","article-title":"GABA is an effective immunomodulatory molecule","volume":"45","author":"Jin","year":"2013","journal-title":"Amino Acids"},{"key":"2022092020043652600_bib28","doi-asserted-by":"publisher","first-page":"19203","DOI":"10.3390\/ijms151019203","article-title":"Glutathionylation of the L-type Ca2+ channel in oxidative stress-induced pathology of the heart","volume":"15","author":"Johnstone","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"2022092020043652600_bib29","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1136\/gut.47.5.632","article-title":"Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans","volume":"47","author":"Keefe","year":"2000","journal-title":"Gut"},{"key":"2022092020043652600_bib30","doi-asserted-by":"publisher","first-page":"4184","DOI":"10.1038\/s41467-018-06487-5","article-title":"GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections","volume":"9","author":"Kim","year":"2018","journal-title":"Nat. Commun."},{"key":"2022092020043652600_bib31","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1126\/science.1112521","article-title":"Mitogenic influence of human R-spondin1 on the intestinal epithelium","volume":"309","author":"Kim","year":"2005","journal-title":"Science"},{"key":"2022092020043652600_bib32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12943-016-0577-4","article-title":"Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation","volume":"16","author":"Lee","year":"2017","journal-title":"Mol. Cancer"},{"key":"2022092020043652600_bib33","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam7610","article-title":"Targeting p53-dependent stem cell loss for intestinal chemoprotection","volume":"10","author":"Leibowitz","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"2022092020043652600_bib34","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1038\/nn1522","article-title":"Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors","volume":"8","author":"Liu","year":"2005","journal-title":"Nat. Neurosci."},{"key":"2022092020043652600_bib35","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1038\/cdd.2016.38","article-title":"\u03b2-Arrestin-2 modulates radiation-induced intestinal crypt progenitor\/stem cell injury","volume":"23","author":"Liu","year":"2016","journal-title":"Cell Death Differ."},{"key":"2022092020043652600_bib36","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc2344","article-title":"Platelet-derived growth factor C signaling is a potential therapeutic target for radiation proctopathy","volume":"13","author":"Lu","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"2022092020043652600_bib37","doi-asserted-by":"publisher","first-page":"987","DOI":"10.3389\/fimmu.2018.00987","article-title":"Activation of GABA(A) receptors in colon epithelium exacerbates acute colitis","volume":"9","author":"Ma","year":"2018","journal-title":"Front. Immunol."},{"key":"2022092020043652600_bib38","doi-asserted-by":"publisher","first-page":"170325","DOI":"10.1155\/2012\/170325","article-title":"New insights into p53 signaling and cancer cell response to DNA damage: Implications for cancer therapy","volume":"2012","author":"Mirzayans","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"2022092020043652600_bib39","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1177\/1534735407305655","article-title":"Do antioxidants interfere with radiation therapy for cancer?","volume":"6","author":"Moss","year":"2007","journal-title":"Integr. Cancer Ther."},{"key":"2022092020043652600_bib40","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1515\/med-2020-0128","article-title":"GABRD promotes progression and predicts poor prognosis in colorectal cancer","volume":"15","author":"Niu","year":"2020","journal-title":"Open Med."},{"key":"2022092020043652600_bib41","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nprot.2006.5","article-title":"The comet assay: A method to measure DNA damage in individual cells","volume":"1","author":"Olive","year":"2006","journal-title":"Nat. Protoc."},{"key":"2022092020043652600_bib42","doi-asserted-by":"publisher","first-page":"a001008","DOI":"10.1101\/cshperspect.a001008","article-title":"TP53 mutations in human cancers: Origins, consequences, and clinical use","volume":"2","author":"Olivier","year":"2010","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"2022092020043652600_bib43","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1124\/pr.108.00505","article-title":"International union of pharmacology. LXX. Subtypes of gamma-aminobutyric Acid(A) receptors: Classification on the basis of subunit composition, pharmacology, and function. Update","volume":"60","author":"Olsen","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"2022092020043652600_bib44","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.am10-3198","article-title":"Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K\/AKT\/p53 axis","volume":"70","author":"Qiu","year":"2010","journal-title":"Cancer Res."},{"key":"2022092020043652600_bib45","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/s0021-9258(19)50929-2","article-title":"Gamma-aminobutyric acid in brain: Its formation from glutamic acid","volume":"187","author":"Roberts","year":"1950","journal-title":"J. Biol. Chem."},{"key":"2022092020043652600_bib46","doi-asserted-by":"publisher","first-page":"805830","DOI":"10.1155\/2012\/805830","article-title":"GABA metabolism and transport: Effects on synaptic efficacy","volume":"2012","author":"Roth","year":"2012","journal-title":"Neural Plast."},{"key":"2022092020043652600_bib47","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1053\/j.gastro.2018.05.033","article-title":"GABA(A) receptor subtypes regulate stress-induced colon inflammation in mice","volume":"155","author":"Seifi","year":"2018","journal-title":"Gastroenterology"},{"key":"2022092020043652600_bib48","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1002\/cam4.686","article-title":"GABAB R\/GSK-3\u03b2\/NF-\u03baB signaling pathway regulates the proliferation of colorectal cancer cells","volume":"5","author":"Shu","year":"2016","journal-title":"Cancer Med."},{"key":"2022092020043652600_bib49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mrrev.2015.07.001","article-title":"Persistent gamma H2AX: A promising molecular marker of DNA damage and aging","volume":"766","author":"Siddiqui","year":"2015","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"2022092020043652600_bib50","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12967-017-1338-x","article-title":"Radioprotective agents to prevent cellular damage due to ionizing radiation","volume":"15","author":"Smith","year":"2017","journal-title":"J. Transl. Med."},{"key":"2022092020043652600_bib51","first-page":"1099","article-title":"Platelet-derived growth factor receptor is a novel modulator of type A gamma-aminobutyric acid-gated ion channels","volume":"48","author":"Valenzuela","year":"1995","journal-title":"Mol. Pharmacol."},{"key":"2022092020043652600_bib52","first-page":"384","article-title":"Intestinal stem cell injury and protection during cancer therapy","volume":"2","author":"Yu","year":"2013","journal-title":"Transl. Cancer Res."},{"key":"2022092020043652600_bib53","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.biopha.2018.07.029","article-title":"Assessment of dose-response relationship of 5-fluorouracil to murine intestinal injury","volume":"106","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"2022092020043652600_bib54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021063118","article-title":"GABAergic synapses suppress intestinal innate immunity via insulin signaling in Caenorhabditis elegans","volume":"118","author":"Zheng","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022092020043652600_bib55","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nature12416","article-title":"Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection","volume":"501","author":"Zhou","year":"2013","journal-title":"Nature"},{"key":"2022092020043652600_bib56","doi-asserted-by":"publisher","first-page":"18416","DOI":"10.1073\/pnas.1906251116","article-title":"The GABA receptor GABRR1 is expressed on and functional in hematopoietic stem cells and megakaryocyte progenitors","volume":"116","author":"Zhu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20220541\/1439097\/jem_20220541.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20220541\/1439097\/jem_20220541.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T20:06:08Z","timestamp":1663704368000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/219\/12\/e20220541\/213480\/Inhibition-of-GABAA-receptors-in-intestinal-stem"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":56,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12,5]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20220541","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]},"article-number":"e20220541"}}