2021
Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH
Maeda H, Ishima Y, Saruwatari J, Mizuta Y, Minayoshi Y, Ichimizu S, Yanagisawa H, Nagasaki T, Yasuda K, Oshiro S, Taura M, McConnell MJ, Oniki K, Sonoda K, Wakayama T, Kinoshita M, Shuto T, Kai H, Tanaka M, Sasaki Y, Iwakiri Y, Otagiri M, Watanabe H, Maruyama T. Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH. Journal Of Controlled Release 2021, 341: 457-474. PMID: 34856227, DOI: 10.1016/j.jconrel.2021.11.039.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntioxidantsHumansKupffer CellsMiceNitric OxideNon-alcoholic Fatty Liver DiseaseConceptsMannose receptor C type 1Treatment of NASHNonalcoholic steatohepatitisKupffer cellsBlood flowNO donorReactive oxygen speciesHepatic blood flowDevelopment of steatohepatitisNASH model miceC type 1Nitric oxide donorOxidative stress-associated pathologiesStress-associated pathologiesCombination therapyHepatoprotective effectModel miceLiver lobeOxide donorType 2Therapeutic potentialType 1Nitric oxidePathological phenotypesSpecific uptake
2020
Lymphatic Dysfunction as a Novel Therapeutic Target in Nonalcoholic Steatohepatitis
Jeong J, Iwakiri Y. Lymphatic Dysfunction as a Novel Therapeutic Target in Nonalcoholic Steatohepatitis. Cellular And Molecular Gastroenterology And Hepatology 2020, 11: 663-664. PMID: 33220266, PMCID: PMC7846486, DOI: 10.1016/j.jcmgh.2020.10.013.Commentaries, Editorials and LettersHumansNon-alcoholic Fatty Liver DiseaseReduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity
Zhang S, Guo F, Yu M, Yang X, Yao Z, Li Q, Wei Z, Feng K, Zeng P, Zhao D, Li X, Zhu Y, Miao QR, Iwakiri Y, Chen Y, Han J, Duan Y. Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity. Journal Of Hepatology 2020, 73: 1482-1495. PMID: 32738448, DOI: 10.1016/j.jhep.2020.07.034.Peer-Reviewed Original ResearchConceptsDiet-induced metabolic disordersHepatic lipid accumulationInsulin sensitivityMetabolic disordersInsulin resistanceNogo expressionNon-alcoholic fatty liver diseaseDiet-induced body weight gainInsulin activityDiet-induced glucose intoleranceLipid accumulationFatty liver diseaseHigh-fructose dietGrowth factor 21Littermate control miceDe novo lipogenesisHigh-carbohydrate dietBody weight gainCarbohydrate-responsive element-binding proteinExpression of ChREBPChREBP activityEndoplasmic reticulum stressMetabolic complicationsGlucose intoleranceLiver disease
2019
Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.Peer-Reviewed Original ResearchConceptsHigh-fat dietSignificant clinical applicabilityHuman nonalcoholic steatohepatitisNonalcoholic steatohepatitisOral digoxinLiver injuryCell subsetsPathway activationMouse modelHigh-fat diet mouse modelLiver injury mouse modelHepatocyte mitochondrial dysfunctionClinical applicabilityDiet mouse modelInjury mouse modelDifferential involvementLarge clinical experienceNLRP3 inflammasome activationSignificant protective effectHIF-1α transactivationHepatic oxidative stress responseHypoxia-inducible factorLiver inflammationHFD miceWide dosage range
2015
Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a
Wang S, Song K, Srivastava R, Dong C, Go G, Li N, Iwakiri Y, Mani A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. The FASEB Journal 2015, 29: 3436-3445. PMID: 25917329, PMCID: PMC4511193, DOI: 10.1096/fj.15-271171.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell Line, TumorCell TransdifferentiationFatty LiverHep G2 CellsHepatocytesHumansLiverLow Density Lipoprotein Receptor-Related Protein-6MiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseProtein BindingProtein Kinase CProtein Kinase C-alphaRho-Associated KinasesSignal TransductionTransforming Growth Factor beta1VimentinWnt Signaling PathwayWnt3A ProteinConceptsNonalcoholic fatty liver diseaseFatty liver diseaseNonalcoholic steatohepatitisLiver diseaseLDL receptor-related protein 6NASH-related liver diseaseMetabolic risk factorsChronic liver diseaseEarly-onset atherosclerosisImportant potential therapeutic targetTGF-β1 activityPotential therapeutic targetDisease pathwaysRas homolog family member ASmooth muscle αFamily member ARisk factorsDisease progressionCommon causeLRP6 knockdownTherapeutic targetWnt3a administrationHepatocyte transdifferentiationDiseaseMuscle α