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Gender-and Age-Group Specific Association of Persistent Organic Pollutants(POPs)Exposure with Diabetes Mellitus:Korean National Environmental Health Survey(KoNEHS)2015−2017

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Environment & Health 2024年第5期2卷 322-331页

作者： Inae Lee Min Joo Kim Sohyeon Choi Young Joo Park Jeongim Park Gökçe Nur Ayaz Gowoon Lee Yoon Hee Cho Hye Li Jeon Chulwoo Lee Gi Jeong Cheon Min Kyong Moon Kyungho Choi Graduate School of Public Health Seoul National UniversitySeoul 08826Republic of Korea Institute of Health and Environment Seoul National UniversitySeoul 08826Republic of Korea Department of Internal medicine Seoul National University College of MedicineSeoul 03080Republic of Korea Seoul National University Hospital Healthcare System Gangnam Center Seoul 06236Republic of Korea Department of Environmental Health Sciences Soonchunhyang UniversityAsan 31538Republic of Korea Department of Molecular medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and TechnologySeoul National UniversitySeoul 08826Republic of Korea Center for Environmental Health Sciences Department of Biomedical and Pharmaceutical SciencesUniversity of MontanaMissoulaMontana 59812United States Environmental Health Research division National Institute of Environmental ResearchMinistry of EnvironmentIncheon 22689Republic of Korea Department of nuclear medicine Seoul National University College of MedicineSeoul 03080Republic of Korea division of Endocrinology Department of Internal MedicineSeoul National University Boramae Medical CenterSeoul 07061Republic of Korea

Exposure to persistent organic pollutants(POPs)has been reported as a potential risk factor for diabetes in ***,effect modifications by sex and age,especially among Asian populations,have seldom been *** the present study,we assessed associations of major POPs exposure including organochlorine pesticides(OCPs),polychlorinated biphenyls(PCBs),and polybrominated diphenyl ethers(PBDEs),with diabetes in Korean adults(n=1,295),a subset of the Korean National Environmental Health Survey(KoNEHS)Cycle 3(2015−2017).In the adult population,serum levels of dichlorodiphenyltrichloroethanes(DDTs)and PCB167 showed an increased odds ratio(OR)for *** stratified by gender,associations became stronger and more consistent in women:In women,serum levels of OCPs including p,p′-DDT,p,p′-dichlorodiphenyldichloroethylene(p,p′-DDE),andΣOCPs and mono-ortho PCBs,such as PCB118 and PCB157,were significantly associated with *** the male participants,however,no significant positive associations were *** stratified by a cutoff age of 50 years,most studied POPs except PBDEs,i.e.,p,p′-DDT,p,p′-DDE,PCB118,PCB157,PCB167,PCB138,and PCB153,showed significant associations with diabetes,in the older *** the younger group,however,no measured POPs showed a significant positive *** of endogenous sex hormones or interaction of POPs on aryl hydrocarbon receptors may partly explain the observed differences by gender and age,although further experimental confirmations should *** findings show that POPs exposure at the current levels is associated with diabetes among general Korean adults,and such associations could be modified by gender and age.

关键词： persistent organic pollutants diabetes age gender toxicity equivalency factor

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Interleukin-1β:Friend or foe for gastrointestinal cancers

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1676-1682页

作者： Kullanat Khawkhiaw Jutatip Panaampon Thanit Imemkamon Charupong Saengboonmee Department of Biochemistry Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Center for Translational medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Cholangiocarcinoma Research Institute Khon Kaen UniversityKhon Kaen 40002Thailand Department of Medical Oncology Dana-Farber Cancer InstituteHarvard Medical SchoolBostonMA 02215United States Department of medicine Harvard Medical SchoolBostonMA 02215United States division of Hematopoiesis Joint Research Center for Human Retrovirus InfectionKumamoto UniversityKumamoto 860-0811Japan Department of medicine Faculty of MedicineKhon Kaen UnivsersityKhon Kaen 40002Thailand

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and ***-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related ***-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting *** studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in *** application of IL-1β inhibitors is also promising for targeted therapy development in some cancer ***,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different *** editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling *** and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

关键词： Cancer Gastrointestinal tract Inflammation Interleukin-1β Tumor microenvironment

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Autoimmune pancreatitis:Cornerstones and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 817-832页

作者： Camilla Gallo Giulia Dispinzieri Nicola Zucchini Pietro Invernizzi Sara Massironi division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy Department of Pathology Fondazione IRCCS San Gerardo dei TintoriMonza 20900Italy

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and *** AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic *** is commonly classified into two *** 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel ***,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical *** clinical manifestations of AIP mainly include painless jaundice and weight *** serum IgG4 levels are particularly characteristic of *** relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic *** mainstay of treatment for AIP is steroid therapy,which is effective in most *** cases might require additional imm-unosuppressive *** review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment *** also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

关键词： Autoimmunity Pancreatitis Autoimmune pancreatitis Immunoglobulin G4 Steroids Relapse

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nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： nuclear receptor coactivator 6 nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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COMPARISON OF VARIOUS CORRELATION ON IRMA FOR CA19-9 AND CA50 IN THE DIGESTIVE SYSTEM TUMOUR

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nuclear Science and Techniques 1990年第4期1卷 234-238页

作者：莫启忠 R.P.Baum A.Hertel G.Hr Shanghai College of Traditional Chinese medicine Shanghai 200032 China nuclear medicine division of radiological centre Frankfurt University Hospital

This paper compared various correlation of IMRA for CA19-9 and CA50 in the digestive system tumour antigen, such as linearity, sensitivity, analytical range, precision as well as storage and stability and so on. And it also determined serum level of CA19- 9 and CA50 of patients with different tumours. The results showed it was well correlated to CA19- 9 and CA50 as a marker of digestive system tumour. Particularly high levels of both markers were found in patients with pancreastic colonic cancer. Therefore it is possible to obtain a higher sensitivity and acceptable specificity by combination with CA19-9 and CA50.

关键词： Tumour marker CA50 CA19- 9 IRMA Solid phase immunoassay Inter- and intraassay variance

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L-Ergothioneine ameliorates MPTP-induced Parkinson's disease in C57BL/6J mice by activating DJ-1

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Food Science and Human Wellness 2024年

作者： Xianshe Meng# Huawen Meng# Shuzeng Hou Zequn Yin Xuerui Wang Ke Gong Feng Zhang Qingshan Li Shuang Zhang Yuanli Chen Xiaoxiao Yang Zhiwei Zhao Chenzhong Liao Yajun Duan Department of Cardiology， the First Affiliated Hospital of USTC， division of Life Sciences and medicine， University of Science and Technology of China Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes， Hefei University of Technology

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. The loss of dopaminergic (DAergic) neurons in the substantia nigra and the decrease of dopamine (DA) levels accelerate the process of PD. L-Ergothioneine (EGT) is a natural antioxidant derived from microorganisms， especially in edible mushrooms. EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients. Therefore， we speculated that EGT could ameliorate PD， and determined its effect on PD development by using 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine (MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium (MPP+)-induced cell models. Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice. Mechanistically， we innovatively revealed that EGT is a key regulator of DJ-1. EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1) axis. Furthermore， it reduced reactive oxygen species (ROS) levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway， which inhibited oxidative stress-induced DAergic neuronal apoptosis. Combined treatment with DJ-1-siRNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus， which significantly decreased the benefits of EGT. Taken together， our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.

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One-neutron stripping process in the^(209)Bi(^(6)Li,^(5)Li)^(210)Bi*reaction reaction

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nuclear Science and Techniques 2024年第6期35卷 120-129页

作者： Gao-Long Zhang Zhen-Wei Jiao Guang-Xin Zhang E.N.Cardozo B.Paes Shi-Peng Hu Jian-Qiang Qian Daniele Mengoni Wei-Wei Qu Cong-Bo Li Yun Zheng Huan-Qiao Zhang Hui-Bin Sun Nan Wang Chun-Lei Zhang J.J.Valiente-Dobón D.Testov M.Mazzocco A.Gozzelino C.Parascandolo D.Pierroutsakou M.La Commara A.Goasduff D.Bazzacco D.R.Napoli F.Galtarossa F.Recchia A.Illana S.Bakes I.Zanon S.Aydin Gde Angelis M.Siciliano R.Menegazzo S.M.Lenzi S.Akkoyun L.F.Canto J.Lubian School of Physics Beihang UniversityBeijing 100191China Sino-French Institute of nuclear Engineering and Technology Sun Yat-Sen UniversityZhuhai 519082China Instituto de Física Universidade Federal Fluminense24210-340 NiteróiRio de JaneiroBrazil Laboratorio TANDAR Comisión Nacional de Energía AtómicaBKNA1650 San MartíınArgentina Institute for Advanced Study in nuclear Energy and Safety Shenzhen UniversityShenzhen 518060China Shenzhen Key Laboratory of Research and Manufacture of High Purity Germanium Materials and Fetectors Shenzhen UniversityShenzhen 518060China INFN Sezione di PadovaPaduaItaly Dipartimento di fisica Astronomia dell’Universita di padova PaduaItaly State Key Laboratory of Radiation medicine and Protection School of Radiation Medicine and ProtectionSoochow UniversitySuzhou 215123China China Institute of Atomic Energy Beijing 102413China The Key Laboratory of Beam Technology and Material Modification of Ministry of Education College of Nuclear Science and TechnologyBeijing Normal UniversityBeijing 100875China Laboratori Nazionali di Legnaro INFN35020 LegnaroItaly INFN Sezione di Napoli80126 NaplesItaly Dipartimento di Farmacia Universitàdi Napoli“Federico II”80131 NaplesItaly Department of Natural and Mathematical Sciences Faculty of EngineeringTarsus University33480 MersinTurkey Physics division Argonne National LaboratoryLemontILUSA Department of Physics Sivas Cumhuriyet UniversitySivasTurkey Instituto de Física Universidade Federal do Rio de JaneiroRio de Janeiro CP 6852821941-972Brazil

One-neutron stripping process between^(6)Li and^(209)Bi was studied at 28,30,and 34 MeV using the in-beamγ-ray spectroscopy ***γ-γcoincident analysis clearly identified twoγ-rays feeding the ground and long-lived isomeric states,which were employed to determine the cross *** one-neutron stripping cross sections were similar to the cross sections of complete fusion in the^(6)Li+^(209)Bi system,but the one-neutron stripping cross sections decreased more gradually at the sub-barrier region.A coupled-reaction-channel calculation was performed to study the detailed reaction mechanism of the one-neutron stripping process in^(6)*** calculations indicated that the first excited state of 5 Li is critical in the actual one-neutron transfer mechanism,and the valence proton of 209Bi can be excited to the low-lying excited state in(^(6)Li,^(5)Li)reaction,unlike in the(d,p)reaction.

关键词： Transfer reaction Weakly bound nuclei Cross section

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Outcomes of combined mitochondria and mesenchymal stem cellsderived exosome therapy in rat acute respiratory distress syndrome and sepsis

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World Journal of Stem Cells 2024年第6期16卷 690-707页

作者： Kun-Chen Lin Wen-Feng Fang Jui-Ning Yeh John Y Chiang Hsin-Ju Chiang Pei-Lin Shao Pei-Hsun Sung Hon-Kan Yip Department of Anesthesiology Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina division of Pulmonary and Critical Care medicine Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiung 83301TaiwanChina Department of Cardiology The First Affiliated Hospital of Jinan UniversityGuangzhou 510630Guangdong ProvinceChina Department of Computer Science and Engineering National Sun Yat-sen UniversityKaohsiung 804201TaiwanChina Department of Healthcare Administration and Medical Informatics Kaohsiung Medical UniversityKaohsiung 80708TaiwanChina School of medicine Chung Shan Medical UniversityTaichung 40201TaiwanChina Department of Nursing Asia UniversityTaichung 41354TaiwanChina division of Cardiology Department of Internal MedicineKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung 83301TaiwanChina Institute for Translational Research in Biomedicine Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina Center for Shockwave medicine and Tissue Engineering Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina Department of Medical Research China Medical University HospitalChina Medical UniversityTaichung 40402TaiwanChina School of medicine College of MedicineChang Gung UniversityTaoyuan 33302TaiwanChina

BACKGROUND The treatment of acute respiratory distress syndrome(ARDS)complicated by sepsis syndrome(SS)remains *** To investigate whether combined adipose-derived mesenchymal-stem-cells(ADMSCs)-derived exosome(EXAD)and exogenous mitochondria(mitoEx)protect the lung from ARDS complicated by *** In vitro study,including L2 cells treated with lipopolysaccharide(LPS)and in vivo study including male-adult-SD rats categorized into groups 1(sham-operated-control),2(ARDS-SS),3(ARDS-SS+EXAD),4(ARDS-SS+mitoEx),and 5(ARDS-SS+EXAD+mitoEx),were included in the present *** In vitro study showed an abundance of mitoEx found in recipient-L2 cells,resulting in significantly higher mitochondrial-cytochrome-C,adenosine triphosphate and relative mitochondrial DNA levels(Pnuclear factor-κB/toll-like receptor(TLR)-4/matrix-metalloproteinase(MMP)-9/oxidative-stress(NOX-1/NOX-2)/apoptosis(cleaved-caspase3/cleaved-poly(ADP-ribose)polymerase)]were significantly attenuated in lipopolysaccharide(LPS)-treated L2 cells with EXAD treatment than without EXAD treatment,whereas the protein expressions of cellular junctions[occluding/β-catenin/zonula occludens(ZO)-1/E-cadherin]exhibited an opposite pattern of inflam-mation(all P<0.001).Animals were euthanized by 72 h post-48 h-ARDS induction,and lung tissues were *** 72 h,flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflam-matory cells(Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+)and albumin were lowest in group 1,highest in group 2,and significantly higher in groups 3 and 4 than in group 5(all P<0.0001),whereas arterial oxygen-saturation(SaO2%)displayed an opposite pattern of albumin among the *** findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers(CD68+/γ-H2AX)displayed an identical pattern of SaO2%among the groups(all P<0.0001).The pro

关键词： Acute respiratory distress syndrome Sepsis syndrome Exosomes Mitochondria Adipose tissue-derived mesenchymal stem cells Inflammation

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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GRK2-YAP signaling is implicated in pulmonary arterial hypertension development

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Chinese Medical Journal 2024年第7期137卷 846-858页

作者： Peng Ye Yunfei Deng Yue Gu Pengfei Liu Jie Luo Jiangqin Pu Jingyu Chen Yu Huang Nanping Wang Yong Ji Shaoliang Chen division of Cardiovascular Molecular Laboratory Third Clinical CollegeNanjing Medical UniversityNanjingJiangsu 210006China division of Cardiovascular Laboratory Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China division of Cardiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China division of Pulmonary Surgery Wuxi People’s HospitalNanjing Medical UniversityWuxiJiangsu 300247China Institute of Vascular medicine The Chinese University of Hong KongHongkong 999077China Health Science Center East China Normal UniversityShanghai 200241China School of Pharmacy Nanjing Medical UniversityNanjingJiangsu 210004China division of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China

Background:Pulmonary arterial hypertension(PAH)is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells(PASMCs),endothelial dysfunction,and extracellular matrix remodeling.G protein-coupled receptor kinase 2(GRK2)plays an important role in the maintenance of vascular tone and blood ***,the role of GRK2 in the pathogenesis of PAH is ***:GRK2 levels were detected in lung tissues from healthy people and PAH patients.C57BL/6 mice,vascular smooth muscle cell-specific Grk2-knockout mice(Grk2^(∆SM22)),and littermate controls(Grk2^(flox/flox))were grouped into control and hypoxia mice(n=8).Pulmonary hypertension(PH)was induced by exposure to chronic hypoxia(10%)combined with injection of the SU5416(cHx/SU).The expression levels of GRK2 and Yes-associated protein(YAP)in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence *** mRNA expression levels of Grk2 and Yes-associated protein(YAP)in PASMCs were quantified with real-time polymerase chain reaction(RT-PCR).Wound-healing assay,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay,and 5-Ethynyl-2′-deoxyuridine(EdU)staining were performed to evaluate the proliferation and migration of ***,the interaction among proteins was detected by immunoprecipitation ***:The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH ***,cHx/SU-induced PH was attenuated in Grk2^(∆SM22) mice compared with littermate *** amelioration of PH in Grk2^(∆SM22) mice was accompanied by reduced pulmonary vascular *** vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration,whereas this effect was severely intensified by overexpression of *** also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs,resulting in excessive PA

关键词： Pulmonary arterial hypertension GRK2 YAP Pulmonary artery smooth muscle cell Hypoxia

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