{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:06:22Z","timestamp":1755799582003,"version":"3.44.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06276","18H04013","22H04922"],"award-info":[{"award-number":["16H06276","18H04013","22H04922"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24gm1210007h0006"],"award-info":[{"award-number":["24gm1210007h0006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Renal fibrosis is a final common pathway for progressive chronic kidney diseases. Immune cell infiltration and production of tumour growth factor\u2010<jats:italic>\u03b2<\/jats:italic> (TGF\u2010<jats:italic>\u03b2<\/jats:italic>) are essential factors for fibrosis development. We examined the role of chondroitin sulfate (CS) proteoglycan, which is one of the main extracellular matrix components induced by TGF\u2010<jats:italic>\u03b2<\/jats:italic> signalling. We also examined CS <jats:italic>N\u2010<\/jats:italic>acetylgalactosaminyltransferase 1 (T1), an enzyme that catalyses the first step of CS\u2010specific synthesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>T1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, genetically lacking <jats:italic>T1<\/jats:italic>, and <jats:italic>T1<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice underwent 5\/6 nephrectomy (Nx) or sham operation. Kidney function, urine marker, mRNA expression, and TGF\u2010<jats:italic>\u03b2<\/jats:italic> signalling were evaluated 1\u2009month after Nx or sham operation. Renal fibrotic area was quantified 3\u2009months later.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both <jats:italic>T1<\/jats:italic><jats:sup>+\/+<\/jats:sup> and <jats:italic>T1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with Nx showed equivalent loss of kidney function; however, a tubular damage marker, upregulation of TGF\u2010<jats:italic>\u03b2<\/jats:italic> and collagen expression, and renal fibrosis were suppressed in <jats:italic>T1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with Nx. Versican, one of the core proteins of CS proteoglycan, was exclusively upregulated in <jats:italic>T1<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice with Nx. Among the versican splicing variants, versican 1 (V1) was expressed in the medullary interstitium of the remnant kidney in <jats:italic>T1<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice. V1 was produced in the interstitial macrophages, fibroblasts\/myofibroblasts, and endothelial cells, whereas TGF\u2010<jats:italic>\u03b2<\/jats:italic> was expressed in fibroblasts\/myofibroblasts. Phosphorylation of the TGF\u2010<jats:italic>\u03b2<\/jats:italic> signalling molecules Smad2\/3 was not induced in <jats:italic>T1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with Nx. In\u00a0vivo administration of TGF\u2010<jats:italic>\u03b2<\/jats:italic> inhibitor into Nx mice reduced <jats:italic>V1<\/jats:italic> and <jats:italic>Tgfb<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>T1 was essential for effective TGF\u2010<jats:italic>\u03b2<\/jats:italic> signalling, V1 upregulation, and subsequent renal fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.70109","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T05:35:22Z","timestamp":1755581722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chondroitin Sulfate <scp><i>N<\/i><\/scp>\u2010Acetylgalactosaminyltransferase 1 Promotes the Progression of Renal Fibrosis Mediated by Versican 1 in Mouse Remnant Kidney"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6396-0055","authenticated-orcid":false,"given":"Yoshikatsu","family":"Kaneko","sequence":"first","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1734-3838","authenticated-orcid":false,"given":"Yuya","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaho","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosei","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology School of Medicine, Aichi Medical University  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihiro","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry and Molecular Cell Biology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiei","family":"Narita","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000054"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.149"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01379-7"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00082"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.11.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3740"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109528"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.06.006"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702299200"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2017.10.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100847"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35412-5"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwaa072"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1814"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155412465073"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112020"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155419846875"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155420953922"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00512"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47419-X"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01764-w"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.712807"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2019.1627220"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2017.1324432"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/11.3.393"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044891"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122912"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.03.011"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010101049"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09321209"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000486398"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488257"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.70109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T23:13:59Z","timestamp":1755645239000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.70109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/nep.70109"],"URL":"https:\/\/doi.org\/10.1111\/nep.70109","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"type":"print","value":"1320-5358"},{"type":"electronic","value":"1440-1797"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2024-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70109"}}