{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:59:00Z","timestamp":1790276340816,"version":"4.1.0"},"reference-count":121,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6818","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL163680"],"award-info":[{"award-number":["HL163680"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99HL179374"],"award-info":[{"award-number":["K99HL179374"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R00HL164962"],"award-info":[{"award-number":["NIH R00HL164962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R35 HL184262"],"award-info":[{"award-number":["NIH R35 HL184262"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL085844"],"award-info":[{"award-number":["R01 HL085844"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL186546"],"award-info":[{"award-number":["R01 HL186546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL170520"],"award-info":[{"award-number":["R01 HL170520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 HL160274"],"award-info":[{"award-number":["U01 HL160274"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R35 GM156286"],"award-info":[{"award-number":["NIH R35 GM156286"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R35 NS137408"],"award-info":[{"award-number":["NIH R35 NS137408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23CDA1050577"],"award-info":[{"award-number":["23CDA1050577"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005188","name":"Tobacco-Related Disease Research Program","doi-asserted-by":"publisher","award":["T34KT7965"],"award-info":[{"award-number":["T34KT7965"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL130020"],"award-info":[{"award-number":["R01 HL130020"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL185054"],"award-info":[{"award-number":["R01 HL185054"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI183953"],"award-info":[{"award-number":["U01 AI183953"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI195484"],"award-info":[{"award-number":["U01 AI195484"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG3 AG097135"],"award-info":[{"award-number":["UG3 AG097135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1 TR006031"],"award-info":[{"award-number":["UM1 TR006031"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","award":["DISC0-18038"],"award-info":[{"award-number":["DISC0-18038"]}],"id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Heart Association","award":["23CDA1050577"],"award-info":[{"award-number":["23CDA1050577"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["AHA 24CDA1276831"],"award-info":[{"award-number":["AHA 24CDA1276831"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["898932"],"award-info":[{"award-number":["898932"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["AHA 23SCEFIA1156132"],"award-info":[{"award-number":["AHA 23SCEFIA1156132"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["NIH R01 HL180515"],"award-info":[{"award-number":["NIH R01 HL180515"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Department of Defense","award":["HT9425-24-1-0504"],"award-info":[{"award-number":["HT9425-24-1-0504"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"<jats:p>Cardiac fibrosis independently predicts adverse outcomes in heart failure (HF), yet no Food and Drug Administration\u2013approved therapy directly targets fibrotic remodeling in the heart. To address this unmet clinical need, we used a multidimensional drug discovery pipeline centered on a human induced pluripotent stem cell (iPSC)\u2013based platform. Through high-throughput screening, we identified CGS15943 (CGS) as the lead antifibrotic compound and validated its activity in human cardiac fibroblasts, three-dimensional engineered heart tissues, and animal models of HF. Mechanistic studies revealed an atypical adenosine receptor (AR)\u2013dependent signaling pathway in which AR subtypes converge on G\u03b2\u03b3 (the \u03b2\u03b3 subunits of heterotrimeric GTP-binding proteins) to activate phosphoinositide 3-kinase (PI3K)\u2013AKT and yes-associated protein (YAP). CGS suppressed this signaling axis, thereby reducing fibrotic gene expression and fibroblast activation. These findings establish AR-driven G\u03b2\u03b3 signaling as a potential therapeutic target for cardiac fibrosis.<\/jats:p>","DOI":"10.1126\/science.aej5896","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:00:41Z","timestamp":1790272841000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Targeting an atypical G protein\u2013coupled receptor signaling pathway for cardiac fibrosis therapy"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-0959","authenticated-orcid":true,"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-5422","authenticated-orcid":true,"given":"Rabindra V.","family":"Shivnaraine","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Greenstone Biosciences, Palo Alto, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9731-8562","authenticated-orcid":true,"given":"Lu","family":"Ren","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7344-150X","authenticated-orcid":true,"given":"Phung N.","family":"Thai","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA."},{"name":"Department of Internal Medicine, University of California, Davis, Davis, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi","family":"Janicot","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cell Biology, Chobanian &amp; Avedisian School of Medicine, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-4825","authenticated-orcid":true,"given":"Wenjuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5399-0074","authenticated-orcid":true,"given":"Rihua","family":"Huang","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-8023","authenticated-orcid":true,"given":"Dirk H.","family":"Siepe","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyi","family":"Tu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2323-7962","authenticated-orcid":true,"given":"Wenqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Maziarz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cell Biology, Chobanian &amp; Avedisian School of Medicine, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0968-501X","authenticated-orcid":true,"given":"Jonathan C.","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-127X","authenticated-orcid":true,"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-3896","authenticated-orcid":true,"given":"Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Department of Physiology and Medicine, Cardiovascular Center and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle H.","family":"Shin","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1303-9954","authenticated-orcid":true,"given":"Hyeonyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-2822","authenticated-orcid":true,"given":"Mark","family":"Chandy","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Greenstone Biosciences, Palo Alto, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-5829","authenticated-orcid":true,"given":"Marian","family":"Kalocsay","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9499-8817","authenticated-orcid":true,"given":"Nipavan","family":"Chiamvimonvat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of California, Davis, Davis, CA, USA."},{"name":"Department of Basic Medical Sciences, Department of Internal Medicine, and Translational Cardiovascular Research Center, University of Arizona College of Medicine \u2013 Phoenix, Phoenix, AZ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-4826","authenticated-orcid":true,"given":"Mikel","family":"Garcia-Marcos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cell Biology, Chobanian &amp; Avedisian School of Medicine, Boston University, Boston, MA, USA."},{"name":"Department of Biology, College of Arts &amp; Sciences, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5958-3990","authenticated-orcid":true,"given":"Brian K.","family":"Kobilka","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-8041","authenticated-orcid":true,"given":"Joseph C.","family":"Wu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Greenstone Biosciences, Palo Alto, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.11.005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2025.07.016"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00716-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa324"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00504-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402582"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01452-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065585"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.042559"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb3673"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.02.012"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.034"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000445"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.178"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.028"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.020"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0553-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315491"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.036"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24676"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2004.03.006"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt338"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005326"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.6.1363"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo1984"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05060-x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08144"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705925"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31603-X"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.337"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.05.015"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118245"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(24)12531-X"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.3c00214"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.02.017"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aab4068"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.109947"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120378"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.041780"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7761854"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301995"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.073072"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-023-02355-0"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaz4003"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj4282"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100325"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34559-0"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1546-z"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.005565"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05759-7"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00019-7"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2012854118"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2011.139"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.302"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.12.009"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.07.011"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00247"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2008-0265"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108504"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00006.2018"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00243"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-274845"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2177"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1937"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070952"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.02.002"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2022.100671"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.01.030"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15103"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021461"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-200907"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-24912-w"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2013.10.023"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.40554"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069114"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.31.4.943"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.630087"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092482"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.06.049"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015080852"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.191600"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01992-2018"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.07.009"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc839"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202401895RR"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.28018"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3955"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2999"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax9276"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504066200"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.154963"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65620"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.14.10443"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.146243"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2021.102492"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314202"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-023-01134-x"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.045161"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900294106"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-02-0133"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.796"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-418687-3.00018-5"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0594"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0133"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2206708119"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_109_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_3_2_110_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_111_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_3_2_112_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_2_113_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_2_114_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku365"},{"key":"e_1_3_2_115_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_3_2_116_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"e_1_3_2_117_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_3_2_118_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_3_2_119_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-3562"},{"key":"e_1_3_2_120_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"e_1_3_2_121_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_3_2_122_2","unstructured":"H. Zhang Targeting an Atypical GPCR Signaling Pathway for Cardiac Fibrosis Therapy Zenodo (2026). 10.5281\/zenodo.21726949"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.aej5896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:01:36Z","timestamp":1790272896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.aej5896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":121,"journal-issue":{"issue":"6818","published-print":{"date-parts":[[2026,9,24]]}},"alternative-id":["10.1126\/science.aej5896"],"URL":"https:\/\/doi.org\/10.1126\/science.aej5896","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"assertion":[{"value":"2026-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaej5896"}}