{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:41:35Z","timestamp":1793353295427,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2019A1515010271"],"award-info":[{"award-number":["2019A1515010271"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Renal interstitial fibrosis (RIF) is a pathological process that fibrotic components are excessively deposited in the renal interstitial space due to kidney injury, resulting in impaired renal function and chronic kidney disease. The molecular mechanisms controlling renal fibrosis are not fully understood. In this present study, we identified Nuclear protein 1 (Nupr1), a transcription factor also called p8, as a novel regulator promoting renal fibrosis. Unilateral ureteral obstruction (UUO) time\u2010dependently induced Nupr1 mRNA and protein expression in mouse kidneys while causing renal damage and fibrosis. Nupr1 deficiency (\n                    <jats:italic>\n                      Nupr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) attenuated the renal tubule dilatation, tubular epithelial cell atrophy, and interstitial collagen accumulation caused by UUO. Consistently,\n                    <jats:italic>\n                      Nupr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    significantly decreased the expression of type I collagen, myofibroblast markers smooth muscle \u03b1\u2010actin (\u03b1\u2010SMA), fibroblast\u2010specific protein 1 (FSP\u20101), and vimentin in mouse kidney that were upregulated by UUO. These results suggest that Nupr1 protein was essential for fibroblast activation and\/or epithelial\u2010mesenchymal transition (EMT) during renal fibrogenesis. Indeed, Nupr1 was indispensable for TGF\u2010\u03b2\u2010induced myofibroblast activation of kidney interstitial NRK\u201049F fibroblasts, multipotent mesenchymal C3H10T1\/2 cells, and the EMT of kidney epithelial NRK\u201052E cells. It appears that Nupr1 mediated TGF\u2010\u03b2\u2010induced \u03b1\u2010SMA expression and collagen synthesis by initiating Smad3 signaling pathway. Importantly, trifluoperazine (TFP), a Nupr1 inhibitor, alleviated UUO\u2010induced renal fibrosis. Taken together, our results demonstrate that Nupr1 promotes renal fibrosis by activating myofibroblast transformation from both fibroblasts and tubular epithelial cells.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000926rr","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T08:35:47Z","timestamp":1613982947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Nupr1 mediates renal fibrosis via activating fibroblast and promoting epithelial\u2010mesenchymal transition"],"prefix":"10.1096","volume":"35","author":[{"given":"Ruimei","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Forensic Medicine Southern Medical University Guangzhou P.R. China"},{"name":"Department of Surgery Medical Pharmacology &amp; Physiology University of Missouri Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashun","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine Southern Medical University Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunpeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Surgery Medical Pharmacology &amp; Physiology University of Missouri Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine Southern Medical University Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enping","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine Southern Medical University Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"L\u00fc","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Southern Medical University Guangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010You","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery Medical Pharmacology &amp; Physiology University of Missouri Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Bing","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine Southern Medical University Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-018-1820-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1300575"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000313946"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3218"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155419849388"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00734.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/12.5.904"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40139-013-0026-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39104"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283414c88"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-016-0020-y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2017.11.019"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13465"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3902"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.51.32360"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-3-25"},{"key":"e_1_2_9_18_1","first-page":"4675","article-title":"Expression of a novel factor in human breast cancer cells with metastatic potential","volume":"59","author":"Ree AH","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00092.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508955103"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102942"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2007.03.011"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0163"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-009-9183-x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3006-x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.11.006"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015080936"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.202747"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-011-1772-6"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3570249"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127223"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39732"},{"key":"e_1_2_9_33_1","first-page":"3278","article-title":"Trifluoperazine induces apoptosis through the upregulation of Bax\/Bcl\u20102 and downregulated phosphorylation of AKT in mesangial cells and improves renal function in lupus nephritis mice","volume":"41","author":"Wang B","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120368"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000926RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202000926RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000926RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T21:28:22Z","timestamp":1761686902000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202000926RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1096\/fj.202000926RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202000926rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]},"assertion":[{"value":"2020-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21381"}}