{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:38:58Z","timestamp":1781534338265,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7254312"],"award-info":[{"award-number":["7254312"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82200762"],"award-info":[{"award-number":["No. 82200762"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170686"],"award-info":[{"award-number":["82170686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M754288"],"award-info":[{"award-number":["2024M754288"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-025-04653-3","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T14:08:31Z","timestamp":1759154911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["MSCs-derived HGF alleviates senescence after AKI by modulating mitoSTAT3-controlled copper flux and respiration"],"prefix":"10.1186","volume":"16","author":[{"given":"Kaiting","family":"Zhuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xumin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"issue":"5","key":"4653_CR1","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/ki.2011.379","volume":"81","author":"SG Coca","year":"2012","unstructured":"Coca SG, Parikh SSCR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81(5):442\u20138.","journal-title":"Kidney Int"},{"issue":"10474","key":"4653_CR2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0140-6736(24)02385-7","volume":"405","author":"M Ostermann","year":"2025","unstructured":"Ostermann M, Lumlertgul N, Jeong R, et al. Acute kidney injury. Lancet. 2025;405(10474):241\u201356.","journal-title":"Lancet"},{"key":"4653_CR3","doi-asserted-by":"crossref","unstructured":"Haberkiewicz O, Lipi\u0144ski P, Starzy\u0144ski RR et al. Decreased expression of the Slc31a1 gene and cytoplasmic relocalization of membrane CTR1 protein in renal epithelial cells: a potent protective mechanism against copper nephrotoxicity in a mouse model of Menkes Disease. Int J Mol Sci. 2022;23(19).","DOI":"10.3390\/ijms231911441"},{"issue":"10","key":"4653_CR4","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1038\/s41401-023-01098-3","volume":"44","author":"SY Zhu","year":"2023","unstructured":"Zhu SY, Zhou WQ, Niu YY, et al. COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity. Acta Pharmacol Sin. 2023;44(10):2091\u2013102.","journal-title":"Acta Pharmacol Sin"},{"issue":"1","key":"4653_CR5","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1152\/physrev.1969.49.1.48","volume":"49","author":"MR Lemberg","year":"1969","unstructured":"Lemberg MR. Cytochrome oxidase. Physiol Rev. 1969;49(1):48\u2013121.","journal-title":"Physiol Rev"},{"issue":"1","key":"4653_CR6","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1186\/s13287-024-04041-3","volume":"15","author":"K Zhuang","year":"2024","unstructured":"Zhuang K, Wang W, Zheng X, et al. MSCs-derived HGF alleviates senescence by inhibiting unopposed mitochondrial fusion-based elongation in post-acute kidney injury. Stem Cell Res Ther. 2024;15(1):438.","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"4653_CR7","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1186\/s13287-021-02468-6","volume":"12","author":"Y He","year":"2021","unstructured":"He Y, Guo X, Lan T, et al. Human umbilical cord-derived mesenchymal stem cells improve the function of liver in rats with acute-on-chronic liver failure via downregulating Notch and Stat1\/Stat3 signaling. Stem Cell Res Ther. 2021;12(1):396.","journal-title":"Stem Cell Res Ther"},{"key":"4653_CR8","doi-asserted-by":"publisher","first-page":"808855","DOI":"10.3389\/fphar.2022.808855","volume":"13","author":"Y Zhao","year":"2022","unstructured":"Zhao Y, Ye W, Wang YD, et al. HGF\/c-Met: A key promoter in liver regeneration. Front Pharmacol. 2022;13:808855.","journal-title":"Front Pharmacol"},{"key":"4653_CR9","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cyto.2016.05.019","volume":"87","author":"DJ Garama","year":"2016","unstructured":"Garama DJ, White CL, Balic JJ, et al. Mitochondrial STAT3: powering up a potent factor. Cytokine. 2016;87:20\u20135.","journal-title":"Cytokine"},{"key":"4653_CR10","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.yjmcc.2018.03.019","volume":"118","author":"G Zhang","year":"2018","unstructured":"Zhang G, Sheng M, Wang J, et al. Zinc improves mitochondrial respiratory function and prevents mitochondrial ROS generation at reperfusion by phosphorylating STAT3 at Ser(727). J Mol Cell Cardiol. 2018;118:169\u201382.","journal-title":"J Mol Cell Cardiol"},{"issue":"5","key":"4653_CR11","first-page":"1019","volume":"52","author":"Y Yan","year":"2023","unstructured":"Yan Y, Xu Y, Chen L, et al. Identification of Lncrna-Mrna networks in Hepg2 cells upon ATP7B knockout and copper accumulation. Iran J Public Health. 2023;52(5):1019\u201330.","journal-title":"Iran J Public Health"},{"key":"4653_CR12","doi-asserted-by":"crossref","unstructured":"Yang H, Zhong C, Tan X et al. Transcriptional responses of copper-transport-related genes ctr1, ctr2 and atox1 and their roles in the regulation of Cu homeostasis in yellow catfish Pelteobagrus Fulvidraco. Int J Mol Sci. 2022;23(20):12243.","DOI":"10.3390\/ijms232012243"},{"issue":"2","key":"4653_CR13","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41580-021-00415-0","volume":"23","author":"ILA Vercellino","year":"2022","unstructured":"Vercellino ILA, Sazanov. The assembly, regulation and function of the mitochondrial respiratory chain. Nat Rev Mol Cell Biol. 2022;23(2):141\u201361.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5","key":"4653_CR14","doi-asserted-by":"publisher","first-page":"107233","DOI":"10.1016\/j.jbc.2024.107233","volume":"300","author":"F Xiao","year":"2024","unstructured":"Xiao F, Jia Y, Zhang S, et al. SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3. J Biol Chem. 2024;300(5):107233.","journal-title":"J Biol Chem"},{"issue":"6664","key":"4653_CR15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/34657","volume":"391","author":"C Boccaccio","year":"1998","unstructured":"Boccaccio C, And\u00f2 M, Tamagnone L, et al. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature. 1998;391(6664):285\u20138.","journal-title":"Nature"},{"issue":"21","key":"4653_CR16","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.1128\/MCB.00541-15","volume":"35","author":"DJ Garama","year":"2015","unstructured":"Garama DJ, Harris TJ, White CL, et al. A synthetic lethal interaction between glutathione synthesis and mitochondrial reactive oxygen species provides a Tumor-Specific vulnerability dependent on STAT3. Mol Cell Biol. 2015;35(21):3646\u201356.","journal-title":"Mol Cell Biol"},{"issue":"6","key":"4653_CR17","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1016\/j.jaci.2021.12.783","volume":"149","author":"L Fu","year":"2022","unstructured":"Fu L, Zhao J, Huang J, et al. A mitochondrial STAT3-methionine metabolism axis promotes ILC2-driven allergic lung inflammation. J Allergy Clin Immunol. 2022;149(6):2091\u2013104.","journal-title":"J Allergy Clin Immunol"},{"key":"4653_CR18","doi-asserted-by":"publisher","first-page":"140247","DOI":"10.1016\/j.chemosphere.2023.140247","volume":"345","author":"X Wei","year":"2023","unstructured":"Wei X, Chen G, Xu Y, et al. Zinc attenuates sulfamethoxazole-induced lipotoxicity by reversing sulfamethoxazole-induced mitochondrial dysfunction and lysosome impairment in a freshwater teleost. Chemosphere. 2023;345:140247.","journal-title":"Chemosphere"},{"issue":"6586","key":"4653_CR19","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1126\/science.abf0529","volume":"375","author":"P Tsvetkov","year":"2022","unstructured":"Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375(6586):1254\u201361.","journal-title":"Science"},{"issue":"1\u20132","key":"4653_CR20","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1023\/A:1007151511817","volume":"209","author":"N Garc\u00eda","year":"2000","unstructured":"Garc\u00eda N, Zazueta C, Carrillo R, et al. Copper sensitizes the mitochondrial permeability transition to carboxytractyloside and oleate. Mol Cell Biochem. 2000;209(1\u20132):119\u201323.","journal-title":"Mol Cell Biochem"},{"issue":"1","key":"4653_CR21","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ejcb.2012.09.002","volume":"92","author":"M Elschami","year":"2013","unstructured":"Elschami M, Scherr M, Philippens B, et al. Reduction of STAT3 expression induces mitochondrial dysfunction and autophagy in cardiac HL-1 cells. Eur J Cell Biol. 2013;92(1):21\u20139.","journal-title":"Eur J Cell Biol"},{"issue":"5","key":"4653_CR22","doi-asserted-by":"publisher","first-page":"4373","DOI":"10.1007\/s11357-024-01119-x","volume":"46","author":"H Cao","year":"2024","unstructured":"Cao H, Xie Q, Luo P, et al. Di-(2-ethylhexyl) phthalate exposure induces premature testicular senescence by disrupting mitochondrial respiratory chain through STAT5B-mitoSTAT3 in Leydig cell. Geroscience. 2024;46(5):4373\u201396.","journal-title":"Geroscience"},{"issue":"11","key":"4653_CR23","doi-asserted-by":"publisher","first-page":"e13996","DOI":"10.1111\/acel.13996","volume":"22","author":"E Zukowski","year":"2023","unstructured":"Zukowski E, Sannella M, Rockhold JD, et al. STAT3 modulates CD4(+) T mitochondrial dynamics and function in aging. Aging Cell. 2023;22(11):e13996.","journal-title":"Aging Cell"},{"issue":"8","key":"4653_CR24","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1038\/cdd.2014.36","volume":"21","author":"JQ Kwong","year":"2014","unstructured":"Kwong JQ, Davis J, Baines CP, et al. Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy. Cell Death Differ. 2014;21(8):1209\u201317.","journal-title":"Cell Death Differ"},{"key":"4653_CR25","doi-asserted-by":"publisher","first-page":"102990","DOI":"10.1016\/j.redox.2023.102990","volume":"69","author":"D Huang","year":"2024","unstructured":"Huang D, Chen L, Ji Q, et al. Lead aggravates alzheimer\u2019s disease pathology via mitochondrial copper accumulation regulated by COX17. Redox Biol. 2024;69:102990.","journal-title":"Redox Biol"},{"issue":"5","key":"4653_CR26","doi-asserted-by":"publisher","first-page":"119734","DOI":"10.1016\/j.bbamcr.2024.119734","volume":"1871","author":"RF de Oliveira","year":"2024","unstructured":"de Oliveira RF, Salazar M, Matos L, et al. High copper levels induce premature senescence in 3T3-L1 preadipocytes. Biochim Biophys Acta Mol Cell Res. 2024;1871(5):119734.","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"4653_CR27","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.redox.2018.03.007","volume":"16","author":"S Masaldan","year":"2018","unstructured":"Masaldan S, Clatworthy SAS, Gamell C, et al. Copper accumulation in senescent cells: interplay between copper transporters and impaired autophagy. Redox Biol. 2018;16:322\u201331.","journal-title":"Redox Biol"},{"issue":"1","key":"4653_CR28","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/s00018-024-05358-1","volume":"81","author":"S Zhu","year":"2024","unstructured":"Zhu S, Niu Y, Zhou W, et al. Mitochondrial copper overload promotes renal fibrosis via inhibiting pyruvate dehydrogenase activity. Cell Mol Life Sci. 2024;81(1):340.","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"4653_CR29","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/s41418-018-0171-y","volume":"26","author":"L Avalle","year":"2019","unstructured":"Avalle L, Camporeale A, Morciano G, et al. STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca(2+) fluxes and apoptotic responses. Cell Death Differ. 2019;26(5):932\u201342.","journal-title":"Cell Death Differ"},{"issue":"5","key":"4653_CR30","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1080\/15548627.2015.1017192","volume":"11","author":"L You","year":"2015","unstructured":"You L, Wang Z, Li H, et al. The role of STAT3 in autophagy. Autophagy. 2015;11(5):729\u201339.","journal-title":"Autophagy"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04653-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04653-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04653-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T14:08:33Z","timestamp":1759154913000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04653-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4653"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04653-3","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"assertion":[{"value":"8 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"hUC-MSCs used in this study were donated by Vcanbio Cell & Gene Engineering Corp. Ltd, which had confirmed that there was initial ethical approval for collection of human cells. The work described has been carried out in accordance with Declaration of Helsinki for experiments involving humans, and that informed consent was obtained for experimentation with human subjects. The animal experiments were conducted in line with the ARRIVE guidelines 2.0. All animal experiments were performed under ethical supervision and approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital in 2022 (Title research: Study on stem cell therapy for acute kidney injury. No. 2022-X18-39. Date of approval: April 18, 2022). This ethical approval also permitted performing experiments using the aforementioned hUC-MSCs.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"526"}}