{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:00:07Z","timestamp":1790344807648,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>The advanced stages of chronic kidney disease (CKD) are difficult to reverse, yet their protein\u2010level pathology remains poorly defined. We analysed the kidney proteome of Pod\u2010TRECK mice, a model of podocyte\u2010driven CKD, at Day 14 and Day 21, representing the progression and late phases, respectively. We then integrated these proteomic data with group\u2010average fold changes from a corresponding time\u2010point transcriptomic dataset generated from separate cohorts of mice using the same model. Although renal function is known to worsen from Day 14 to Day 21 in this model, the bulk\u2010kidney proteome changed only modestly over this interval. Concordance between protein and transcript fold changes also decreased, indicating that late disease progression involves protein\u2010level changes that are not fully reflected by steady\u2010state mRNA abundance. This late\u2010phase signature was distributed across multiple protein groups. NR3C2, the mineralocorticoid receptor, was upregulated at the protein level without a corresponding change in transcript abundance, as further validated by immunohistochemistry. Being the pharmacological target of finerenone, NR3C2 represents a clinically relevant protein\u2010level change that transcriptomic profiling alone would miss. A subset of plasma\u2010derived proteins also accumulated in injured mouse kidneys without matching local transcript induction. A similar pattern was observed in human CKD kidney tissue, while related plasma proteins were reduced in patients with rapid CKD progression. Complement C5 was one prominent member of this candidate plasma\u2010protein\u2010handling signature. Together, these findings show that the late phase of podocyte\u2010driven CKD involves distributed protein\u2010level remodelling, including an RNA\u2010discordant increase in NR3C2 protein and a candidate plasma\u2010protein\u2010handling signature.<\/jats:p>","DOI":"10.1111\/febs.70748","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:15:56Z","timestamp":1790342156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated proteomic\u2013transcriptomic profiling identifies\n                    <scp>NR3C2<\/scp>\n                    up\u2010regulation and a candidate plasma\u2010protein\u2010handling signature in chronic podocyte injury"],"prefix":"10.1111","author":[{"given":"Koichi","family":"Ito","sequence":"first","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koyuki","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Kono","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeru","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuya","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Applied Genomics Kazusa DNA Research Institute  Kisarazu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7971-3024","authenticated-orcid":false,"given":"Nobuya","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-074216"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.17002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15765"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac7071"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0204"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31772-9"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01802-x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.149"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1369\/0022155419849388","article-title":"Extracellular matrix in kidney fibrosis: more than just a scaffold","volume":"67","author":"B\u00fclow RD","year":"2019","journal-title":"J Histochem Cytochem"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.014"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3185"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0258-4"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70333"},{"key":"e_1_2_12_16_1","unstructured":"Kidney Precision Medicine Project(2024)Atlas Explorer v1.0 regional proteomics data. Kidney Precision Medicine Project.10.48698\/mg7h\u2010bc51"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13098-019-0430-1","article-title":"Characterization of low molecular weight urinary proteins at varying time intervals in type 2 diabetes mellitus and diabetic nephropathy patients","volume":"11","author":"Patel DN","year":"2019","journal-title":"Diabetol Metab Syndr"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.034"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709945200"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1117995","article-title":"Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics","volume":"14","author":"Wang D","year":"2023","journal-title":"Front Immunol"},{"key":"e_1_2_12_21_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12882-018-1139-3","article-title":"Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity","volume":"19","author":"Guo Z","year":"2018","journal-title":"BMC Nephrol"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.46.5.465"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V104685"},{"key":"e_1_2_12_24_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12967-015-0463-7","article-title":"Urine fetuin\u2010a is a biomarker of autosomal dominant polycystic kidney disease progression","volume":"13","author":"Piazzon N","year":"2015","journal-title":"J Transl Med"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12014-023-09405-0","article-title":"Proteomic signature associated with chronic kidney disease progression identified by data\u2010independent acquisition mass spectrometry","volume":"20","author":"Ram\u00edrez Medina CR","year":"2023","journal-title":"Clin Proteomics"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.006"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110956"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.11.003"},{"key":"e_1_2_12_30_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2024.1478697","article-title":"Tubulointerstitial injury in proteinuric chronic kidney diseases","volume":"11","author":"Cortinovis M","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2015.11.007"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.4.F562"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu261"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006040377"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.01.039"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02385"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.10.046"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016111179"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00966"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12710-9"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0620"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054862"},{"key":"e_1_2_12_43_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1161\/CIRCGENETICS.113.000654","article-title":"Plasma concentrations of afamin are associated with the prevalence and development of metabolic syndrome","volume":"7","author":"Kronenberg F","year":"2014","journal-title":"Circ Cardiovasc Genet"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100745"},{"key":"e_1_2_12_45_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abd3359","article-title":"Molecular characterization of the human kidney interstitium in health and disease","volume":"7","author":"Barwinska D","year":"2021","journal-title":"Sci Adv"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70748","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.70748","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70748","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:15:59Z","timestamp":1790342159000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.70748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":45,"alternative-id":["10.1111\/febs.70748"],"URL":"https:\/\/doi.org\/10.1111\/febs.70748","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"2026-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"febs.70748"}}