{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:04:19Z","timestamp":1790762659293,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Discovery"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tubular epithelial dedifferentiation and loss of polarity are early pathological events in obstructive nephropathy and critically contribute to progressive renal fibrosis. Human umbilical cord mesenchymal stem cell\u2013derived exosomes (HucMSC\u2010Exos) have shown therapeutic potential for kidney injury, yet the mechanisms by which they preserve epithelial identity remain unclear. Mafb, a transcription factor essential for renal epithelial differentiation, has been implicated in epithelial homeostasis, but its role in adult obstructive injury and its regulation by exosomes are unknown. Here, a unilateral ureteral obstruction (UUO) mouse model was used to evaluate early tubular injury and the effects of HucMSC\u2010Exos. UUO induced marked epithelial damage characterized by decreased E\u2010cadherin, increased vimentin and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) expression, and disruption of epithelial polarity, whereas HucMSC\u2010Exo administration significantly ameliorated these alterations. Mafb expression was profoundly downregulated in UUO kidneys but was effectively restored following exosome treatment. In vitro,\n                    <jats:italic>Mafb<\/jats:italic>\n                    knockdown in Human renal proximal tubular epithelial (HK\u20102) cells markedly aggravated TGF\u2010\u03b21\u2013induced dedifferentiation, confirming its protective role in epithelial integrity. Analysis of\n                    <jats:italic>Mafb<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    embryonic kidneys demonstrated severe developmental defects and loss of polarity markers, highlighting the essential function of\n                    <jats:italic>Mafb<\/jats:italic>\n                    in renal epithelium. Importantly, HucMSC\u2010Exos rescued\u00a0epithelial marker expression even in\n                    <jats:italic>Mafb<\/jats:italic>\n                    \u2010silenced cells, suggesting both\n                    <jats:italic>Mafb<\/jats:italic>\n                    \u2010dependent and independent mechanisms. These findings identify\n                    <jats:italic>Mafb<\/jats:italic>\n                    as a key regulator of tubular epithelial homeostasis and reveal that HucMSC\u2010Exos attenuate early renal injury partly through Mafb restoration.\n                  <\/jats:p>","DOI":"10.1002\/pdi3.70059","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:36:58Z","timestamp":1782848218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HucMSC\u2010Derived Exosomes Preserve Mafb\u2010Dependent Tubular Epithelial Identity and Suppress Dedifferentiation in Obstructive Nephropathy"],"prefix":"10.1002","volume":"4","author":[{"given":"Zhuocheng","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders  Chongqing China"},{"name":"Chongqing Key Laboratory of Structural Birth Defect and Reconstruction  Chongqing China"},{"name":"Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders  Chongqing China"},{"name":"Chongqing Key Laboratory of Structural Birth Defect and Reconstruction  Chongqing China"},{"name":"Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders  Chongqing China"},{"name":"Chongqing Key Laboratory of Structural Birth Defect and Reconstruction  Chongqing China"},{"name":"Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders  Chongqing China"},{"name":"Chongqing Key Laboratory of Structural Birth Defect and Reconstruction  Chongqing China"},{"name":"Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8488-2967","authenticated-orcid":false,"given":"Deying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders  Chongqing China"},{"name":"Chongqing Key Laboratory of Structural Birth Defect and Reconstruction  Chongqing China"},{"name":"Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders  Chongqing China"},{"name":"Chongqing Key Laboratory of Structural Birth Defect and Reconstruction  Chongqing China"},{"name":"Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.62820"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12203"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2022\u201000080"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.11817\/j.issn.1672\u20107347.2021.201008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1981798"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577\u2010021\u201000617\u2010w"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1049\/nbt2.12071"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658\u2010023\u201000425\u20100"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175523"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114450"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112315"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010026\u201004893\u2010x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2021.06.008"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.00001\u201006"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.9336\u201022"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010023\u201001468\u20103"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2024.101432"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001374\u20100"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.09.033"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.10.020"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.02.025"}],"container-title":["Pediatric Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pdi3.70059","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pdi3.70059","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pdi3.70059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:41:06Z","timestamp":1790761266000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pdi3.70059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/pdi3.70059"],"URL":"https:\/\/doi.org\/10.1002\/pdi3.70059","archive":["Portico"],"relation":{},"ISSN":["2835-558X","2835-5598"],"issn-type":[{"value":"2835-558X","type":"print"},{"value":"2835-5598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"2026-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70059"}}