2022
TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk
Bhat N, Esteghamat F, Chaube BK, Gunawardhana K, Mani M, Thames C, Jain D, Ginsberg HN, Fernandes‐Hernando C, Mani A. TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk. The FASEB Journal 2022, 36: e22185. PMID: 35133032, PMCID: PMC9624374, DOI: 10.1096/fj.202101607r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsCholesterol 7-alpha-HydroxylaseFibroblast Growth FactorsHomeostasisIleumLipid MetabolismLiverLow Density Lipoprotein Receptor-Related Protein-6MiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseTranscription Factor 7-Like 2 ProteinConceptsGut-liver crosstalkBile synthesisDiet-induced fatty liver diseaseSmall intestineHepatic bile saltIntestinal lipid uptakePlasma bile saltsFatty liver diseaseTreatment of NASHColorectal cancer cellsBile saltsConditional knockout modelHuman NASHFatty liverLiver diseaseFXR activationClinical trialsEnterohepatic circulationTranscription factor TCF4Fl/Hepatic levelsBile acidsEndocrine regulatorLipid uptakeIntestinal epithelium
2018
The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome
Abou Ziki M, Mani A. The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome. Nutrition Research 2018, 70: 18-25. PMID: 30049588, PMCID: PMC6320319, DOI: 10.1016/j.nutres.2018.06.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFatty LiverHumansLipid MetabolismLiverLiver CirrhosisLow Density Lipoprotein Receptor-Related Protein-6Metabolic SyndromeMuscle, Smooth, VascularReceptor, InsulinReceptors, LDLTranscription Factor 7-Like 2 ProteinWnt Signaling PathwayConceptsMetabolic syndromeLow density lipoprotein clearanceVascular smooth muscle proliferationEnd-organ complicationsCanonical WntSmooth muscle proliferationLow-density lipoproteinDe novo lipogenesisInsulin receptor expressionTranscription factor 7Growth factor βRas homolog gene family member AExtracellular matrix depositionCardiometabolic abnormalitiesLiver inflammationFamily member AInsulin resistanceLipoprotein clearanceLiver fatHepatic fibrosisSevere manifestationsLDL receptor-related protein 6Receptor expressionCardiovascular diseaseMuscle proliferation
2015
Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease
Srivastava R, Zhang J, Go GW, Narayanan A, Nottoli TP, Mani A. Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease. Cell Reports 2015, 13: 746-759. PMID: 26489464, PMCID: PMC4626307, DOI: 10.1016/j.celrep.2015.09.028.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell PlasticityCells, CulturedCoronary Artery DiseaseHumansLow Density Lipoprotein Receptor-Related Protein-6MiceMice, Mutant StrainsMyocytes, Smooth MuscleTranscription Factor 7-Like 2 ProteinConceptsCoronary artery diseaseLRP6 activityArtery diseaseObstructive coronary artery diseaseHigh-fat dietVascular smooth muscle cell differentiationMuscle cell plasticitySmooth muscle cell differentiationAtherosclerotic burdenMedial hyperplasiaCarotid injuryArterial diseaseVascular obstructionNeointima formationTherapeutic targetWnt3a administrationIntact WntVSMC differentiationKnockout backgroundDiseaseMiceVessel wallNon-canonical WntCoreceptor LRP6Cell plasticity
2014
The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue
Go GW, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, Ginsberg HN, Mani A. The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue. Cell Metabolism 2014, 19: 209-220. PMID: 24506864, PMCID: PMC3920193, DOI: 10.1016/j.cmet.2013.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCells, CulturedFatty LiverHepatocytesHyperlipidemiasLow Density Lipoprotein Receptor-Related Protein-6Mechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceModels, BiologicalMultiprotein ComplexesMutationNon-alcoholic Fatty Liver DiseaseTOR Serine-Threonine KinasesWnt3A ProteinConceptsHepatic de novo lipogenesisFatty liver diseaseElevated plasma LDLTreatment of hyperlipidemiaSp1-dependent activationCholesterol biosynthesisDe novo lipogenesisAtherogenic lipid disordersMolecular genetic basisLiver diseaseFatty liverLDL levelsPlasma lipidsTG levelsLipid disordersPlasma TGPlasma LDLNovo lipogenesisHyperlipidemiaCombined HyperlipidemiaGenetic basisWnt coreceptorNonconservative mutationsAltered expressionPrimary hepatocytes
2011
Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation
Keramati AR, Singh R, Lin A, Faramarzi S, Ye ZJ, Mane S, Tellides G, Lifton RP, Mani A. Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 1914-1918. PMID: 21245321, PMCID: PMC3033290, DOI: 10.1073/pnas.1019443108.Peer-Reviewed Original ResearchMeSH KeywordsAtherosclerosisCell ProliferationCyclin D1HumansImmunohistochemistryLDL-Receptor Related ProteinsLow Density Lipoprotein Receptor-Related Protein-6Muscle, Smooth, VascularPlatelet-Derived Growth FactorReceptor, Platelet-Derived Growth Factor betaRNA, MessengerSignal TransductionConceptsVascular smooth muscle cell proliferationSmooth muscle cell proliferationLDL receptor-related protein 6Muscle cell proliferationEarly atherosclerosisHuman atherosclerotic coronary arteriesCell proliferationAtherosclerotic coronary arteriesPDGF receptor βPDGF-dependent regulationCoronary arterySmooth muscleVSMC proliferationReceptor βSMC proliferationCell cycle activityAtherosclerosisKey mediatorCritical modulatorProtein 6PDGF SignalingDifferential effectsProliferationFurther investigationCell cycle