{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:47:37Z","timestamp":1773827257491,"version":"3.50.1"},"reference-count":31,"publisher":"Walter de Gruyter GmbH","issue":"8-9","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Shenzhen Science and Technology Program","award":["JCYJ20230807110911023"],"award-info":[{"award-number":["JCYJ20230807110911023"]}]},{"name":"Futian Healthcare Research Project","award":["FTWS2023016"],"award-info":[{"award-number":["FTWS2023016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                    has been used for a long time to treat autoimmune diseases. Its toxic side effects limit its clinical application. Mitophagy plays a protective role in various diseases. TANK-binding kinase 1 (TBK1) is a mitophagy-promoting molecule. This study aimed to investigate whether TBK1 could alleviate triptolide (TP)-induced nephrotoxicity by regulating mitophagy. To establish TP-induced nephrotoxic injury in animal model, 16\u00a0Sprague-Dawley rats were administered with TP by gavage, then renal tissues were collected for hematoxylin and eosin (HE) staining, western blotting and immunofluorescence analysis. To investigate whether up-regulation of TBK1 could alleviate TP-induced nephrotoxic injury and the specific mechanism, HK-2\u202fcells were cultured\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    , transfected with TBK1-overexpression recombinant lentivirus, then treated with TP. Western blotting, immunofluorescence, flow cytometry, multifunctional microplate detector were used to detect the relevant molecules. Here we found that TP caused kidney function damage, declined mitophagy levels, decreased the expression of TBK1 and mitophagy-related proteins in rats. TP stimulation decreased cell viability, mitochondrial membrane potential, mitophagy-protein, the formation of mito-autophagosomes and mito-autophagolysosomes in HK-2\u202fcells. Upregulating TBK1 could reverse these damages. In summary, TP-induced cell injury had decreased mitophagy levels. Up-regulating TBK1 could increase mitophagy and further alleviate TP-induced cell injury.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2024-0141","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T11:08:46Z","timestamp":1747220926000},"page":"391-406","source":"Crossref","is-referenced-by-count":1,"title":["TBK1 alleviates triptolide-induced nephrotoxic injury by up-regulating mitophagy in HK2 cells"],"prefix":"10.1515","volume":"406","author":[{"given":"Xinxin","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Nephrology , 575842 The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qionghui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology , 575842 The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaohui","family":"He","sequence":"additional","affiliation":[{"name":"Department of Urology , The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology , 575842 The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology , 575842 The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youjian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology , The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiecheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology , 575842 The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-3600","authenticated-orcid":false,"given":"Lang-Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nephrology , 575842 The Eighth Affiliated Hospital, Sun Yat-Sen University , Shenzhen , Guangdong , 518033 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"2025121816163025025_j_hsz-2024-0141_ref_001","doi-asserted-by":"crossref","unstructured":"Choi, G.E., Lee, H.J., Chae, C.W., Cho, J.H., Jung, Y.H., Kim, J.S., Kim, S.Y., Lim, J.R., and Han, H.J. 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FASEB J. 34: 6284\u20136301, https:\/\/doi.org\/10.1096\/fj.201903051r.","DOI":"10.1096\/fj.201903051R"},{"key":"2025121816163025025_j_hsz-2024-0141_ref_021","doi-asserted-by":"crossref","unstructured":"Shen, Q., Wang, J., Yuan, Z., Jiang, Z., Shu, T., Xu, D., He, J., Zhang, L., and Huang, X. (2019). Key role of organic cation transporter 2 for the nephrotoxicity effect of triptolide in rheumatoid arthritis. Int. Immunopharmacol. 77: 105959, https:\/\/doi.org\/10.1016\/j.intimp.2019.105959.","DOI":"10.1016\/j.intimp.2019.105959"},{"key":"2025121816163025025_j_hsz-2024-0141_ref_022","doi-asserted-by":"crossref","unstructured":"Vargas, J.N.S., Wang, C., Bunker, E., Hao, L., Maric, D., Schiavo, G., Randow, F., and Youle, R.J. (2019). Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol. 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Toxicity of triptolide and the molecular mechanisms involved. Biomed. Pharmacother. 90: 531\u2013541, https:\/\/doi.org\/10.1016\/j.biopha.2017.04.003.","DOI":"10.1016\/j.biopha.2017.04.003"},{"key":"2025121816163025025_j_hsz-2024-0141_ref_028","doi-asserted-by":"crossref","unstructured":"Xie, W., Jin, S., Zhang, C., Yang, S., Wu, Y., Zhao, Y., Songyang, Z., and Cui, J. (2022). Selective autophagy controls the stability of TBK1 via NEDD4 to balance host defense. Cell Death Differ. 29: 40\u201353, https:\/\/doi.org\/10.1038\/s41418-021-00833-9.","DOI":"10.1038\/s41418-021-00833-9"},{"key":"2025121816163025025_j_hsz-2024-0141_ref_029","doi-asserted-by":"crossref","unstructured":"Yang, F., Zhuo, L., Ananda, S., Sun, T., Li, S., and Liu, L. (2011). Role of reactive oxygen species in triptolide-induced apoptosis of renal tubular cells and renal injury in rats. J.\u00a0Huazhong Univ. Sci Technol. Med. 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