{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:27:12Z","timestamp":1793582832900,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cisplatin causes nephrotoxicity by accumulating in renal tubular epithelial cells (RTECs). Astragaloside IV (ASIV) shows renoprotective potential, but its mechanisms remain poorly understood. Cisplatin induced nephrotoxicity was established in 8\u2010week\u2010old male C57BL\/6 mice via intraperitoneal administration of cisplatin at 20\u2009mg\/kg for 48\u2009h. For in\u00a0vitro studies, HK\u20102 human proximal tubular epithelial cells were exposed to 50\u2009\u03bcM cisplatin for 24\u2009h. Multi\u2010omics approaches were employed to identify novel mechanisms by which ASIV ameliorates cisplatin\u2010induced proximal tubular injury. ASIV markedly reduced serum creatinine and urea nitrogen levels in mice, and ameliorated cisplatin\u2010induced proximal tubular injury both in\u00a0vivo and in\u00a0vitro. Moreover, ASIV restored mitochondrial damage, upregulated protein expression of PGC\u20101\u03b1, TOMM20, and PINK1 in RTECs. Mechanistically, RNA\u2010seq and scRNA\u2010seq revealed that cisplatin predominantly affected ADRA1A\u2010mediated mitochondrial biogenesis and mitophagy in proximal tubular cells, accompanied by suppression of the AMPK\/FOXO3A pathway. Notably, ASIV upregulated ADRA1A expression, thereby facilitating AMPK and FOXO3A phosphorylation and consequently enhancing mitochondrial biogenesis and mitophagy. Furthermore, dabuzalgron (a selective ADRA1A agonist) recapitulated the protective effects of ASIV. In contrast, the renoprotective action of ASIV against cisplatin\u2010induced proximal tubular injury was largely abrogated by the ADRA1A antagonist tamsulosin in\u00a0vivo and by ADRA1A\u2010specific siRNA in\u00a0vitro. These findings identify ASIV as a highly promising renoprotective agent that upregulates ADRA1A expression and activates the AMPK\/FOXO3A axis to enhance mitochondrial biogenesis and mitophagy, thereby counteracting cisplatin\u2010induced proximal tubular injury.<\/jats:p>","DOI":"10.1096\/fj.202602118r","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:40:22Z","timestamp":1788424822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ASIV<\/scp>\n                    Attenuates Cisplatin\u2010Induced Proximal Tubular Injury by Enhancing Mitochondrial Biogenesis and Mitophagy Through the\n                    <scp>ADRA1A<\/scp>\n                    \/\n                    <scp>AMPK<\/scp>\n                    \/\n                    <scp>FOXO3A<\/scp>\n                    Pathway"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1475-2049","authenticated-orcid":false,"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Nephrology Department Chongqing Traditional Chinese Medicine Hospital  Chongqing China"},{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Peng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Wei","sequence":"additional","affiliation":[{"name":"Nephrology Department Chongqing Traditional 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