ArticleCirculation2015
Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.
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Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39citing papers in PubMed
5.6field-weighted citation impact, top 4% of its field
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39 citing papers in PubMed, 71 citations in OpenAlex.
- Air pollution and adverse birth outcomes: a narrative review of epidemiological and mechanistic findings.Journal of environmental health science & engineering · 2026Review
- Placental SNV rs8192446 in theFrontiers in physiology · 2026Article
- Dynamic shifts in trophoblast nucleos(t)ide metabolism, transport, and adenosine signaling during gestation and preterm birth.Scientific reports · 2025Article
- The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?Heliyon · 2024Article
- Metabolomic analysis of the human placenta reveals perturbations in amino acids, purine metabolites, and small organic acids in spontaneous preterm birth.EXCLI journal · 2024Article
- Pathomechanisms of Prenatally Programmed Adult Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta.Frontiers in cell and developmental biology · 2023Article
- Gestational diabetes mellitus placentas exhibit epimutations at placental development genes.Epigenetics · 2022Article
- Evaluation of CD39, CD73, HIF-1α, and their related miRNAs expression in decidua of preeclampsia cases compared to healthy pregnant women.Molecular biology reports · 2022Article
- Integrative exposomic, transcriptomic, epigenomic analyses of human placental samples links understudied chemicals to preeclampsia.Environment international · 2022Article
- Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review.International journal of molecular sciences · 2022Review
- Epigenetic processes during preeclampsia and effects on fetal development and chronic health.Clinical science (London, England : 1979) · 2021Review
- Placenta-derived IL-32β activates neutrophils to promote preeclampsia development.Cellular & molecular immunology · 2021Article
- The association of MOV10 polymorphism and expression levels with preeclampsia in the Chinese Han population.Molecular genetics & genomic medicine · 2021Article
- Low-Dose Aspirin Prevents Kidney Damage in LPS-Induced Preeclampsia by Inhibiting the WNT5A and NF-κB Signaling Pathways.Frontiers in endocrinology · 2021Article
- NLRP3 inflammasome: a new therapeutic target for high-risk reproductive disorders?Chinese medical journal · 2020Article
- Maternal erythrocyte ENT1-mediated AMPK activation counteracts placental hypoxia and supports fetal growth.JCI insight · 2020Article
- Reciprocal upregulation of hypoxia-inducible factor-1α and persistently enhanced placental adenosine signaling contribute to the pathogenesis of preeclampsia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Role of the NLRP3 Inflammasome in Preeclampsia.Frontiers in endocrinology · 2020Review
- Management of ADA-Deficient SCID Patient on Adagen During Pregnancy.Journal of clinical immunology · 2019Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Takayuki IriyamaFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Kaiqi SunFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Nicholas F ParchimFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Jessica LiFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Cheng ZhaoFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Anren SongFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Laura A HartFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Sean C BlackwellFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Baha M SibaiFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Lee-Nien L ChanFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Teh-Sheng ChanFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
M John HicksFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Michael R BlackburnFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Rodney E KellemsFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.).
Yang XiaFrom Departments of Biochemistry and Molecular Biology (T.I., K.S., N.F.P., J.L., C.Z., A.S., M.R.B., R.E.K., Y.X.) and Department of Obstetrics, Gynecology, and Reproductive Sciences (L.A.H., S.C.B., B.M.S.), University of Texas Medical School at Houston: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan (T.I.); Graduate School of Biomedical Sciences, University of Texas, Houston (K.S., N.F.P., M.R.B, R.E.K., Y.X.); Department of Urology (C.Z.), Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, (L-N. L.C., T.-S.C.); and Department of Pathology, Texas Children's Hospital, Houston (M.J.H.). yang.xia@uth.tmc.edu.
The University of Texas Medical Branch at Galveston · USUniversity of Houston · USXiangya Hospital Central South University · CNCentral South University · CN
Funding
Trangenic Mouse Breeding CoreP01HL114457 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ZHANG, YUJIN · 2013 to 2017
$10.0MPURINE METABOLISM AT THE MATERNAL/FETAL INTERFACER01HD034130 · NICHD · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KELLEMS, RODNEY E · 1996 to 2012
$2.8MAutoantibodies in Preeclampsia: Pre-symptomatic markers and therapeutic targetsRC4HD067977 · NICHD · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KELLEMS, RODNEY E, XIA, YANG · 2010 to 2010
$1.8MMetabolites, Sickle Cell Disease, and Novel TherapeuticsR01HL113574 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI XIA, YANG · 2013 to 2016
$1.5MAdenosine Signaling, Priapism and Sickle Cell DiseaseR01DK083559 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI XIA, YANG · 2009 to 2012
$1.3MAT1 Receptor Activating Autoantibodies and PreeclampsiaR01HL076558 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI XIA, YANG · 2005 to 2008
$1.0MTransgenic Mouse Model for Adenosine-induced AsthmaR01HL073430 · NHLBI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI CHAN, TEHSHENG · 2002 to 2003
$371kAngiotensin Receptor Autoantibodies and PreeclampsiaR56HD034130 · NICHD · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KELLEMS, RODNEY E · 2007 to 2007
$371kNHLBI NIH HHS HL119549NHLBI NIH HHS HL73430NHLBI NIH HHS P01 HL114457NHLBI NIH HHS R01 HL073430NHLBI NIH HHS R01 HL076558NHLBI NIH HHS R01 HL113574NICHD NIH HHS HD34130NICHD NIH HHS R01 HD034130NICHD NIH HHS R56 HD034130NICHD NIH HHS RC4 HD067977NICHD NIH HHS RC4HD067977NIDDK NIH HHS R01 DK083559
Abstract
backgroundPreeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. METHODS AND
resultsUsing 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia.
conclusionsWe determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets.
Indexed as
5'-NucleotidaseAdenosineAdenosine DeaminaseAdultAnimalsAutoantibodiesDisease Models, AnimalFemaleFetal Growth RetardationGene DeletionHumansMice, KnockoutPlacentaPre-EclampsiaPregnancyReceptor, Adenosine A2B5'-NucleotidaseAdenosineAdenosine DeaminaseAutoantibodiesFLT1 protein, humanReceptor, Adenosine A2BVascular Endothelial Growth Factor Receptor-1adenosinehypertensionmodels, animalpreeclampsiapregnancy
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