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We found that the expression of transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2)\u2010activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen\u2010activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB\/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20\u00a0mg\/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin\u2010induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down\u2010regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in\u00a0vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.<\/jats:p>","DOI":"10.1111\/jcmm.13585","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T11:59:18Z","timestamp":1520251158000},"page":"2908-2921","source":"Crossref","is-referenced-by-count":49,"title":["TAK1 mediates excessive autophagy via p38 and ERK in cisplatin\u2010induced acute kidney injury"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-8092","authenticated-orcid":false,"given":"Jun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First People's Hospital of Foshan Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youling","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Panyu Central Hospital 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