{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:49:09Z","timestamp":1767898149593,"version":"3.49.0"},"reference-count":142,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2017ZX10203207-004-005"],"award-info":[{"award-number":["2017ZX10203207-004-005"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672884"],"award-info":[{"award-number":["81672884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2 are the main targets of antiangiogenic therapies, and proteinuria is one of the common adverse events associated with the inhibition of the VEGFA\/VEGFR2 pathway. The proteinuric kidney damage induced by VEGFR2 tyrosine kinase inhibitors (TKIs) is characterized by podocyte foot process effacement. TKI therapy promotes the formation of abnormal endothelial\u2012podocyte crosstalk, which plays a key role in TKI-induced podocyte injury and proteinuric nephropathy. This review article summarizes the underlying mechanism by which the abnormal endothelial\u2012podocyte crosstalk mediates podocyte injury and discusses the possible molecules and signal pathways involved in abnormal endothelial\u2012podocyte crosstalk. What is more, we highlight the molecules involved in podocyte injury and determine the essential roles of Rac1 and Cdc42; this provides evidence for exploring the abnormal endothelial\u2012podocyte crosstalk in TKI-induced nephrotoxicity.<\/jats:p>","DOI":"10.3390\/cells10040869","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Abnormal Crosstalk between Endothelial Cells and Podocytes Mediates Tyrosine Kinase Inhibitor (TKI)-Induced Nephrotoxicity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2626-3955","authenticated-orcid":false,"given":"Xiaoying","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute &amp; Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7954-0522","authenticated-orcid":false,"given":"Su","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute &amp; Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8759-4395","authenticated-orcid":false,"given":"Ti","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute &amp; Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0140-6736(15)01088-0","article-title":"Antiangiogenic therapy in oncology: Current status and future directions","volume":"388","author":"Jayson","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1681\/ASN.2018080853","article-title":"Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities","volume":"30","author":"Estrada","year":"2019","journal-title":"J. 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