{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:00:20Z","timestamp":1786132820110,"version":"build-2736575974"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","funder":[{"name":"Key program of the Natural Science Foundation of China","award":["No.82530025, 82030023"],"award-info":[{"award-number":["No.82530025, 82030023"]}]},{"DOI":"10.13039\/501100001809","name":"Joint Funds of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No.U22A20279"],"award-info":[{"award-number":["No.U22A20279"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Excellent Youth Fund Program","award":["No.82322012"],"award-info":[{"award-number":["No.82322012"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC2502500\/2022YFC2502501"],"award-info":[{"award-number":["2022YFC2502500\/2022YFC2502501"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No.82300778"],"award-info":[{"award-number":["No.82300778"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chongqing Graduate Innovation Program","award":["CYB23291"],"award-info":[{"award-number":["CYB23291"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Platelet-activating factor receptor contributed to renal tubular epithelial cells G2\/M arrest through suppressing mouse double minute 2\u2013mediated p53 ubiquitin degradation in AKI-to-CKD transition.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Phosphatidylethanolamine (18:0\/18:1) served as a novel endogenous ligand of platelet-activating factor receptor, inducing the downstream signaling.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>WAY-639497, a small-molecule platelet-activating factor receptor antagonist identified by virtual screening, mitigated renal tubular epithelial cells G2\/M arrest and AKI-to-CKD transition.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>AKI represents a critical clinical complication with a high propensity of progression to CKD, yet effective therapies remain limited. G protein\u2013coupled receptors mediate diverse pathophysiological processes and are promising therapeutic targets. Here, we investigated the role of platelet-activating factor receptor (PTAFR), a lipophilic G protein\u2013coupled receptor, in AKI-to-CKD transition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A mouse model of ischemia-reperfusion injury (IRI)\u2013induced AKI was built by bilateral renal artery clamping. The phenotypic role of PTAFR in renal tubular epithelial cells (RTECs) after AKI was investigated in tubule-specific PTAFR-deficiency mice. The functional and molecular mechanisms were determined by transcriptomic profiling, flow cytometry, coimmunoprecipitation, Western blotting, and immunofluorescence. Lipidomic analysis and biological experiments were used to identify the endogenous ligand of PTAFR. The translational potential of PTAFR was evaluated by structure-based high-throughput virtual screening of a small-molecule inhibitor\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of PTAFR was upregulated in RTECs after AKI\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Tubule-specific depletion of PTAFR alleviated IRI-induced RTEC injury and kidney fibrosis after AKI. Mechanistically, PTAFR promoted RTECs G2\/M arrest by suppressing mouse double minute 2\u2013mediated p53 ubiquitin degradation. Phosphatidylethanolamine (18:0\/18:1) was identified as a novel PTAFR endogenous ligand inducing RTECs G2\/M arrest. Urinary phosphatidylethanolamine (18:0\/18:1) was correlated with kidney dysfunction and was able to effectively distinguish patients with AKI from healthy controls. High-throughput virtual screening identified WAY-639497, a small-molecule PTAFR antagonist, that was able to mitigate IRI-induced RTEC injury and kidney fibrosis after AKI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PTAFR promoted tubular epithelial cell G2\/M arrest by inhibiting mouse double minute 2\u2013mediated p53 ubiquitin degradation and further contributed AKI-to-CKD transition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001132","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T16:08:16Z","timestamp":1779898096000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Role of Lipid Signaling by Platelet-Activating Factor Receptor in Tubular Epithelial Cells in Acute Kidney Injury-to-CKD Transition"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-4751","authenticated-orcid":false,"given":"Liangjing","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-1652","authenticated-orcid":false,"given":"Wang","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-9206","authenticated-orcid":false,"given":"Qigang","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5479-4323","authenticated-orcid":false,"given":"Fugang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2430-3711","authenticated-orcid":false,"given":"Jiachuan","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-1111","authenticated-orcid":false,"given":"Yinghui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0996-854X","authenticated-orcid":false,"given":"Ling","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3511-5935","authenticated-orcid":false,"given":"Yaqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9379-1424","authenticated-orcid":false,"given":"Shuiqin","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9750-3285","authenticated-orcid":false,"given":"Jinghong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"issue":"1","key":"B1-20260806","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-021-00284-z","article-title":"Acute 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