2023
Antibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner
Salvi P, Shaughnessy M, Sumigray K, Cowles R. Antibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner. AJP Gastrointestinal And Liver Physiology 2023, 325: g80-g91. PMID: 37158470, DOI: 10.1152/ajpgi.00113.2022.Peer-Reviewed Original ResearchConceptsSerotonin activitySERT protein expressionSerotonin potentiationEpithelial proliferationSerotonin transporterEndogenous serotoninVillus heightMicrobial depletionIntestinal epithelial growthProtein expressionEpithelial growthSerotonin-dependent mechanismIntestinal villus heightSmall intestine resultsIntestinal surface areaSmall intestinal villiSmall intestinal cryptsIntestinal pathologyPara-chlorophenylalanineISC numbersSerotonin synthesisIntestinal homeostasisEpithelial expressionMouse modelAnimal models
2022
Jejunoileal mucosal growth in mice with a limited microbiome
Shaughnessy MP, Park CJ, Salvi PS, Cowles RA. Jejunoileal mucosal growth in mice with a limited microbiome. PLOS ONE 2022, 17: e0266251. PMID: 35349599, PMCID: PMC8963542, DOI: 10.1371/journal.pone.0266251.Peer-Reviewed Original ResearchConceptsIntestinal mucosal growthMucosal surface areaSmall intestinal mucosal growthCrypt proliferation indexCONV miceGF miceMucosal growthVillus heightEnteral antibioticsCrypt depthCell proportionSmall intestinal villus heightGerm-free miceBroad-spectrum antibioticsConventional floraIntestinal villus heightGerm-free conditionsEnteral administrationMucosal homeostasisGnotobiotic miceProliferation indexEnterocyte proliferationMiceTaller villiGF conditions
2021
Butyrate and the Intestinal Epithelium: Modulation of Proliferation and Inflammation in Homeostasis and Disease
Salvi PS, Cowles RA. Butyrate and the Intestinal Epithelium: Modulation of Proliferation and Inflammation in Homeostasis and Disease. Cells 2021, 10: 1775. PMID: 34359944, PMCID: PMC8304699, DOI: 10.3390/cells10071775.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAnti-proliferative effectsIntestinal stem cellsTolerogenic dendritic cellsAnti-inflammatory cytokinesEpithelial cellsInflammatory bowel diseaseMicrobial metabolite butyrateStem cellsApparent protective effectButyrate-producing bacteriaCellular fuelRole of butyrateCrypt base stem cellsModulation of proliferationButyrate paradoxMalabsorptive statesBowel diseaseDendritic cellsEpithelial inflammationColonic neoplasiaIntestinal microbiomeProtective effectIntestinal neoplasiaIntestinal lumenEpithelial proliferationSerotonin as a Mitogen in the Gastrointestinal Tract: Revisiting a Familiar Molecule in a New Role
Shah PA, Park CJ, Shaughnessy MP, Cowles RA. Serotonin as a Mitogen in the Gastrointestinal Tract: Revisiting a Familiar Molecule in a New Role. Cellular And Molecular Gastroenterology And Hepatology 2021, 12: 1093-1104. PMID: 34022423, PMCID: PMC8350061, DOI: 10.1016/j.jcmgh.2021.05.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnteric nervous systemSerotonin receptorsGI tractPotentiation of serotoninInflammatory bowel diseaseVascular smooth muscleIntestinal epithelial proliferationIntestinal crypt cellsBody's serotoninMalabsorptive conditionsIntestinal injuryEnteric neuronsIntestinal motilityBowel diseaseIntestinal inflammationEnterochromaffin cellsGI diseaseSerotonergic neuronsMuscarinic receptorsCholinergic signalingSerotonin synthesisGastrointestinal systemGastrointestinal tractIntestinal mucosaSmooth muscle
2020
Mucosal characteristics vary across developmental stages in the small intestine of C57BL/6J mice
Park CJ, Shaughnessy MP, Cowles RA. Mucosal characteristics vary across developmental stages in the small intestine of C57BL/6J mice. Life Sciences 2020, 260: 118428. PMID: 32931798, DOI: 10.1016/j.lfs.2020.118428.Peer-Reviewed Original ResearchThe M1 muscarinic acetylcholine receptor in the crypt stem cell compartment mediates intestinal mucosal growth
Greig CJ, Armenia SJ, Cowles RA. The M1 muscarinic acetylcholine receptor in the crypt stem cell compartment mediates intestinal mucosal growth. Experimental Biology And Medicine 2020, 245: 1194-1199. PMID: 32611198, PMCID: PMC7437377, DOI: 10.1177/1535370220938375.Peer-Reviewed Original ResearchConceptsMuscarinic acetylcholine receptorsM1 muscarinic acetylcholine receptorAcetylcholine receptorsStem cell compartmentPotential future therapeutic targetsCell compartmentIntestinal mucosal homeostasisIntestinal mucosal growthFuture therapeutic targetsMucosal homeostasisMucosal growthTherapeutic targetSpecific subtypesProliferative parametersReceptorsFuture studiesDemonstrate increasesCritical roleNovel informationCompartmentsSubtypes
2019
Potentiated serotonin signaling in serotonin re‐uptake transporter knockout mice increases enterocyte mass and small intestinal absorptive function
Greig CJ, Zhang L, Cowles RA. Potentiated serotonin signaling in serotonin re‐uptake transporter knockout mice increases enterocyte mass and small intestinal absorptive function. Physiological Reports 2019, 7: e14278. PMID: 31724827, PMCID: PMC6854605, DOI: 10.14814/phy2.14278.Peer-Reviewed Original ResearchConceptsIntestinal absorptive functionEnterocyte massCrypt proliferation indexSmall intestineAbsorptive functionDistal bowelSmall bowelCrypt depthSERT knockoutVillus heightProliferative parametersSmall intestinal absorptive functionPlasma citrulline levelsCrypt cell proliferationPeptide absorptionSignificant increaseMucosal surface areaAttractive therapeutic targetFunctional intestinal mucosaWT miceCitrulline levelsPlasma citrullineSerotonin systemIntestinal mucosaLuminal instillationPotentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine
Park CJ, Armenia SJ, Shaughnessy MP, Greig CJ, Cowles RA. Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine. Journal Of Pediatric Surgery 2019, 54: 1245-1249. PMID: 30879746, DOI: 10.1016/j.jpedsurg.2019.02.027.Peer-Reviewed Original ResearchConceptsPotentiation of serotoninSmall intestineMucosal growthLipid absorptionSmall intestinal mucosal growthMucosal growth factorsSerotonin reuptake transporterSERT knockout miceDistal small intestineIntestinal mucosal growthCrypt cell proliferationT-testMucosal surface areaMurine small intestineStudent's t-testEnteric serotoninIntestinal failureIntestinal adaptationReuptake transporterDeficient miceWT animalsIntestinal homeostasisFatty acid analogueCrypt depthVillus heightOrally Dosed Citalopram Stimulates Small Intestinal Mucosal Growth
Zhang L, Greig CJ, Cowles RA. Orally Dosed Citalopram Stimulates Small Intestinal Mucosal Growth. Journal Of Surgical Research 2019, 236: 326-331. PMID: 30694773, DOI: 10.1016/j.jss.2018.11.033.Peer-Reviewed Original ResearchConceptsMucosal surface areaSelective serotonin reuptake inhibitorsSerotonin reuptake inhibitorsIntestinal mucosal growthVillus heightVillus widthD citalopramReuptake inhibitorsMucosal growthCrypt depthCrypt widthSmall intestinal mucosal growthShort bowel syndromeT-testSerious intestinal disordersStudent's t-testOral agentsBowel syndromeOral therapyEnteral administrationC57BL/6 miceIleal segmentIntestinal disordersDay 21Day 7
2018
Retracing our STEPs: Four decades of progress in intestinal lengthening procedures for short bowel syndrome
Greig CJ, Oh PS, Gross ER, Cowles RA. Retracing our STEPs: Four decades of progress in intestinal lengthening procedures for short bowel syndrome. The American Journal Of Surgery 2018, 217: 772-782. PMID: 30514435, DOI: 10.1016/j.amjsurg.2018.11.025.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsShort bowel syndromeBowel syndromeReversed intestinal segmentInnovative new treatmentsBowel dilationIntestinal rehabilitationIntestinal failureBowel lengthSurgical managementBacterial overgrowthIntestinal adaptationColonic transpositionPatient outcomesSurgical techniqueLengthening surgeryIntestinal segmentsArtificial valvesNew treatmentsSyndromeCare paradigmPoor motilityBirthOutcomesTransit timeLong termPotentiation of serotonin signaling protects against intestinal ischemia and reperfusion injury in mice
Tackett JJ, Gandotra N, Bamdad MC, Muise ED, Cowles RA. Potentiation of serotonin signaling protects against intestinal ischemia and reperfusion injury in mice. Neurogastroenterology & Motility 2018, 31: e13498. PMID: 30394002, DOI: 10.1111/nmo.13498.Peer-Reviewed Original ResearchConceptsSerotonin re-uptake transporterWild-type littermatesIntestinal ischemiaEnterocyte proliferationMucosal injurySuperior mesenteric artery occlusionPotentiation of serotoninMesenteric artery occlusionRe-uptake transporterChi-squared testEnteric serotoninSMA occlusionArtery occlusionR injuryReperfusion injuryEpithelial injuryMucosal protectionEnteroendocrine cellsGoblet cellsIschemiaInjurySSRIsMiceSerotoninCellular compositionThe 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances Carbohydrate Absorption in the Ileum of the Mouse
Park CJ, Armenia SJ, Zhang L, Cowles RA. The 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances Carbohydrate Absorption in the Ileum of the Mouse. Journal Of Gastrointestinal Surgery 2018, 23: 1198-1205. PMID: 30109470, DOI: 10.1007/s11605-018-3907-6.Peer-Reviewed Original ResearchConceptsDistal small bowelD-xylose absorptionCrypt cell proliferationSmall intestineMurine small intestineSmall bowelMucosal growthSpecific agonistCrypt depthGlucose absorptionIntestinal mucosal surface areaAdult wild-type miceMucosal growth factorsPotentiation of serotoninReceptor agonist prucaloprideDistal small intestineCell proliferationIntestinal mucosal growthWild-type miceReceptor-specific agonistsMiddle small intestineMucosal surface areaEnteric serotoninOral gavageCarbohydrate absorptionMucosal homeostasis is altered in the ileum of gnotobiotic mice
Greig CJ, Alper A, Goodman AL, Cowles RA. Mucosal homeostasis is altered in the ileum of gnotobiotic mice. Journal Of Surgical Research 2018, 231: 331-337. PMID: 30278949, DOI: 10.1016/j.jss.2018.05.055.Peer-Reviewed Original ResearchConceptsGnotobiotic miceMucosal homeostasisGastrointestinal tractCrypt depthVillus heightDistal ileal segmentConventional floraFuture therapeutic strategiesGnotobiotic mouse modelMarkers of proliferationIleal segmentMucosal restorationAkkermansia muciniphilaMouse modelTherapeutic strategiesAdult miceCF miceDisease pathogenesisHistologic sectionsMiceEscherichia coli MG1655IleumNormal physiologyGnotobiotic groupFurther studies
2017
Muscarinic acetylcholine receptors participate in small intestinal mucosal homeostasis
Greig CJ, Cowles RA. Muscarinic acetylcholine receptors participate in small intestinal mucosal homeostasis. Journal Of Pediatric Surgery 2017, 52: 1031-1034. PMID: 28359586, DOI: 10.1016/j.jpedsurg.2017.03.037.Peer-Reviewed Original ResearchConceptsCrypt proliferation indexIntestinal mucosal homeostasisMuscarinic acetylcholine receptorsMucosal homeostasisIleal mucosaAcetylcholine receptorsDistal ileal segmentCholinergic nervous systemWild-type miceCrypt cell proliferationCrypt base stem cellsFunctional mucosaMAChR subtypesMuscarinic signalingIleal segmentCrypt depthProliferation indexNervous systemVillus heightMucosal morphometryMucosaHistologic sectionsMiceMouse linesEpithelial cell typesImproved capacity to evaluate changes in intestinal mucosal surface area using mathematical modeling
Greig CJ, Cowles RA. Improved capacity to evaluate changes in intestinal mucosal surface area using mathematical modeling. Microscopy Research And Technique 2017, 80: 793-798. PMID: 28295852, DOI: 10.1002/jemt.22866.Peer-Reviewed Original ResearchConceptsMucosal surface areaIntestinal mucosal surface areaVillus heightCrypt widthMucosal growthSelective serotonin reuptakeIntestinal mucosal growthEffects of interventionsFunctional intestinal mucosaEnhanced serotoninBowel diameterSerotonin reuptakeIntestinal mucosaMouse modelIleal sectionsTransporter moleculesMorphometric measuresComprehensive assessmentSSRIsMorphometric parametersMucosaSerotoninStandard measuresTherapyReuptake
2016
Distribution of muscarinic acetylcholine receptor subtypes in the murine small intestine
Muise ED, Gandotra N, Tackett JJ, Bamdad MC, Cowles RA. Distribution of muscarinic acetylcholine receptor subtypes in the murine small intestine. Life Sciences 2016, 169: 6-10. PMID: 27866962, DOI: 10.1016/j.lfs.2016.10.030.Peer-Reviewed Original ResearchConceptsSmall intestineReceptor subtypesMuscarinic acetylcholine receptor subtypesShort bowel syndromeEffects of acetylcholineStem cell compartmentMuscarinic receptor subtypesAcetylcholine receptor subtypesSmall intestinal mucosaPotential therapeutic targetMurine small intestineCell compartmentSpecific mAChRBowel syndromeCholinergic pathwaysMyenteric plexusAnatomic distributionMuscarinic receptorsEntire alimentary tractIntestinal diseaseIntestinal mucosaEnterocyte turnoverIntestinal growthTherapeutic targetCrypt basesEnhanced serotonin signaling stimulates ordered intestinal mucosal growth
Tackett JJ, Gandotra N, Bamdad MC, Muise ED, Cowles RA. Enhanced serotonin signaling stimulates ordered intestinal mucosal growth. Journal Of Surgical Research 2016, 208: 198-203. PMID: 27993209, DOI: 10.1016/j.jss.2016.09.036.Peer-Reviewed Original ResearchEnhanced serotonin signaling increases intestinal neuroplasticity
Greig CJ, Gandotra N, Tackett JJ, Bamdad MC, Cowles RA. Enhanced serotonin signaling increases intestinal neuroplasticity. Journal Of Surgical Research 2016, 206: 151-158. PMID: 27916355, DOI: 10.1016/j.jss.2016.07.021.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsIntestinal mucosal growthSERT knockoutMucosal growthEnterocyte proliferationEnteric nervous systemSerotonin reuptake inhibitorsMassive bowel resectionSerotonin reuptake transporterAge-matched WTGAP-43 expressionWild-type miceSynthesis inhibitionMarkers of neuroplasticityImportant regulatorReversal of effectsEpithelial cell compartmentWestern blot analysisBowel resectionReuptake inhibitorsWT miceReuptake transporterMucosal homeostasisIntestinal segmentsCrypt depth
2012
Neuronal Serotonin Regulates Growth of the Intestinal Mucosa in Mice
Gross ER, Gershon MD, Margolis KG, Gertsberg ZV, Li Z, Cowles RA. Neuronal Serotonin Regulates Growth of the Intestinal Mucosa in Mice. Gastroenterology 2012, 143: 408-417.e2. PMID: 22609381, PMCID: PMC3687781, DOI: 10.1053/j.gastro.2012.05.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCholine O-AcetyltransferaseCholinergic NeuronsEnterochromaffin CellsIntestinal MucosaKetanserinMaleMiceMice, Inbred C57BLMice, KnockoutMuscarinic AntagonistsReceptor, Serotonin, 5-HT2AScopolamineSelective Serotonin Reuptake InhibitorsSerotonergic NeuronsSerotoninSerotonin AntagonistsSerotonin Plasma Membrane Transport ProteinsTryptophan HydroxylaseConceptsSelective serotonin re-uptake inhibitorsSerotonin re-uptake inhibitorsRe-uptake inhibitorsWild-type miceIntestinal mucosaSerotonin re-uptake transporterCholinergic submucosal neuronsIntestinal mucosal epitheliumRe-uptake transporterTryptophan hydroxylase 1Tryptophan hydroxylase 2Submucosal neuronsCholinergic neuronsCholine acetyltransferaseNeuronal serotoninMucosal growthMucosal epitheliumMucosal cellsSERT knockoutEpithelial proliferationAbstractTextMiceHydroxylase 2MucosaNeural precursors
2004
Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells
Segura BJ, Zhang W, Xiao L, Turner D, Cowles RA, Logsdon C, Mulholland MW. Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells. Journal Of Surgical Research 2004, 116: 42-54. PMID: 14732348, DOI: 10.1016/s0022-4804(03)00281-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCalciumCalcium ChannelsCalcium SignalingCulture TechniquesDose-Response Relationship, DrugDrug Administration ScheduleEnzyme ActivationGuinea PigsImmunohistochemistryInositol 1,4,5-Trisphosphate ReceptorsLysophospholipidsMyenteric PlexusNeurogliaPertussis ToxinReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledRNA, MessengerSphingolipidsSphingosineType C PhospholipasesConceptsSignal transduction cascadeEnteric nervous systemEnteric gliaLipid lysophosphatidic acidMajor cell typesRT-PCR analysisTransduction cascadeGlial cellsNervous systemEDG-1Trisphosphate receptorCalcium signalingLysophosphatidic acidCell typesExtracellular receptorsPhospholipase CEdg-3Enteric glial cellsBioactive lipidsEdg-5S1P effectsSphingomyelin metabolitesDigestive activityImmunocytochemical analysisEnteric neurons