{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:17:40Z","timestamp":1791433060128,"version":"4.3.3"},"reference-count":84,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"12","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,3,21]]},"abstract":"<jats:p>\n            Genome-wide association studies (GWAS) have identified loci associated with kidney diseases, but the causal variants, genes, and pathways involved remain elusive. Here, we identified a kidney disease gene called pancreatic progenitor cell differentiation and proliferation factor (PPDPF) through integrating GWAS on kidney function and multiomic analysis. PPDPF was predominantly expressed in healthy proximal tubules of human and mouse kidneys via single-cell analysis. Further investigations revealed that PPDPF functioned as a thiol-disulfide oxidoreductase to maintain cellular NAD\n            <jats:sup>+<\/jats:sup>\n            levels. Deficiency in PPDPF disrupted NAD\n            <jats:sup>+<\/jats:sup>\n            and mitochondrial homeostasis by impairing the activities of nicotinamide mononucleotide adenylyl transferases (NMNATs), thereby compromising the function of proximal tubules during injuries. Consequently, knockout of PPDPF notably accelerated the progression of chronic kidney disease (CKD) in mouse models induced by aging, chemical exposure, and obstruction. These findings strongly support targeting PPDPF as a potential therapy for kidney fibrosis, offering possibilities for future CKD interventions.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adr8648","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T18:00:13Z","timestamp":1742407213000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8967-0223","authenticated-orcid":true,"given":"Xiaoliang","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Urology, Children\u2019s Hospital of Fudan University, Shanghai, 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1661-6110","authenticated-orcid":true,"given":"Yi","family":"Zhong","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4446-8724","authenticated-orcid":true,"given":"Rui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Children\u2019s Hospital of Fudan University, Shanghai, 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5979-8297","authenticated-orcid":true,"given":"Qihui","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4623-0153","authenticated-orcid":true,"given":"Dexin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-7561","authenticated-orcid":true,"given":"Wubing","family":"Ding","sequence":"additional","affiliation":[{"name":"Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengbo","family":"Zhong","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Lin","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Yao","sequence":"additional","affiliation":[{"name":"Qingdao Innovation and Development Center, Harbin Engineering University, Qingdao, Shandong, 266000, China."},{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, Heilongjiang, 150001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-6491","authenticated-orcid":true,"given":"Qingxun","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, 200444, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-7534","authenticated-orcid":true,"given":"Xiaofei","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, 17164, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5104-5386","authenticated-orcid":true,"given":"Guofeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Nie","sequence":"additional","affiliation":[{"name":"Biobank of Peking University First Hospital, Peking University First Hospital, Peking University, Beijing, 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-8493","authenticated-orcid":true,"given":"Dali","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-416X","authenticated-orcid":true,"given":"Hongquan","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Urology, Children\u2019s Hospital of Fudan University, Shanghai, 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-270X","authenticated-orcid":true,"given":"Yuting","family":"Guan","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China."},{"name":"Chongqing Key Laboratory of Precision Optics, Chongqing Institute of East China Normal University, Chongqing, 401120, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.35636"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.377"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10023"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0407-x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11704-w"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01097-w"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.10.012"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.11.011"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01200-7"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00553-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-022-02701-y"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.169"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116995"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.314"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-022-02418-3"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202202448"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22266-1"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24491-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0194-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00909-9"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2020.100034"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2085-0"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37691-7"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.09.026"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-020-02025-y"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31772-9"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35297-z"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908706116"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05769-3"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.01.017"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.171"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419139"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.02.017"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.04.009"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9496-0_12"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21018"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2017.03.014"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03828-1"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-440X(95)80010-7"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.053"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051454398"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9187-7_1"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0014-2956.2004.04282.x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/s121115907"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.03.012"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0216-6"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23285-8"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00512.2015"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00385.2019"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-020-0398-3"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202309234"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37450-8"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015020225"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep26235"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.09.014"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29988-w"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.152330"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0645-6"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.07.009"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17184"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00761-7"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016040385"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi4862"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.09.013"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe9985"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12970-021-00442-4"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ19-0313"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.11.001"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4609"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb6242"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09407-3"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.09.019"},{"key":"e_1_3_2_76_2","first-page":"e1646","article-title":"Gastrointestinal side effects of antiarrhythmic medications: A review of current literature","volume":"9","author":"Amjad W.","year":"2017","unstructured":"W. Amjad, W. Qureshi, A. Farooq, U. Sohail, S. Khatoon, S. Pervaiz, P. Narra, S. M. Hasan, F. Ali, A. Ullah, S. Guttmann, Gastrointestinal side effects of antiarrhythmic medications: A review of current literature. Cureus 9, e1646 (2017).","journal-title":"Cureus"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112340"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2018.10.019"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.095"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201506039"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25377-x"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6101"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpmo.21"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep17517"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adr8648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T18:01:54Z","timestamp":1742407314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adr8648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":84,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,3,21]]}},"alternative-id":["10.1126\/sciadv.adr8648"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adr8648","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"assertion":[{"value":"2024-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadr8648"}}