{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:14:53Z","timestamp":1781133293275,"version":"3.54.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Renal interstitial fibrosis (RIF) is an important manifestation of Diabetic nephropathy (DN) progression. Non-POU domain containing octamer-binding protein (NONO) is crucial in fibrosis in cardiovascular diseases, but its role in DN fibrosis remains unclear. This study explores the expression of NONO in DN and its correlation with Matrix Metalloproteinase-9 (MMP-9, as an important regulator of fibrosis), renal fibrosis, and prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty patients with type 2 diabetes mellitus (T2DM) with pathologically confirmed DN were included, divided into early DN group (n=20) and late DN group (n=20). 6 normal renal tissue as control group. HE, Masson staining, immunohistochemical staining and Immunofluorescence double staining were performed. The correlation between NONO expression levels and MMP-9 as well as clinical pathological data was analyzed. Cox regression analysis and Kaplan-Meier survival curves were used to evaluate the relationship between renal tissue NONO expression levels and DN prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with control group, NONO expression levels in renal tissues of DN patient were increased, and the late DN group was higher than the early DN group (<jats:italic>P<\/jats:italic>&amp;lt;0.05). NONO and MMP-9 expression were positively correlated with multiple clinical and Fibrosis-related pathological indicators, and NONO expression was positively correlated with MMP-9(<jats:italic>P<\/jats:italic>&amp;lt;0.05). Patients with high renal NONO expression had lower kidney progression-free survival rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NONO expression levels correlate positively with MMP-9, collagen and renal damage indicators in renal tissues of DN patients. High NONO expression is linked to poor renal prognosis in DN. NONO may contribute to renal tissue fibrosis in DN by regulating MMP-9 levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1652391","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:15:27Z","timestamp":1760415327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation on the relationship between renal NONO expression, fibrosis and prognosis in diabetic nephropathy"],"prefix":"10.3389","volume":"16","author":[{"given":"Shuang","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyuan","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingli","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI165654","article-title":"Molecular pathways that drive diabetic kidney disease","volume":"133","author":"Mohandes","year":"2023","journal-title":"J Clin Invest"},{"key":"B2","doi-asserted-by":"publisher","first-page":"A8","DOI":"10.1053\/j.ajkd.2024.01.001","article-title":"US renal data system 2023 annual data report: epidemiology of kidney disease in the United States","volume":"83","author":"Johansen","year":"2024","journal-title":"Am J Kidney Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-017-6755-9","article-title":"Diabetic nephropathy: a tangled web to unweave","volume":"31","author":"Magee","year":"2017","journal-title":"Cardiovasc Drugs Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13969","article-title":"Pathophysiologic mechanisms in diabetic kidney disease: A focus on current and future therapeutic targets","author":"Barrera-Chimal","year":"2020","journal-title":"Diabetes Obes Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dci23-0030","article-title":"Diabetic nephropathy: update on pillars of therapy slowing progression","volume":"46","author":"Naaman","year":"2023","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1093\/nar\/gkw271","article-title":"The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold","volume":"44","author":"Knott","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/his.12434","article-title":"Decreased expression of P54(nrb)\/NonO correlates with collagen deposition and fibrosis in human aortic dissection","volume":"65","author":"Ren","year":"2014","journal-title":"Histopathology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.yjmcc.2019.10.004","article-title":"Deficiency of NONO is associated with impaired cardiac function and fibrosis in mice","volume":"137","author":"Xu","year":"2019","journal-title":"J Mol Cell Cardiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14613","article-title":"Silencing of NONO inhibits abdominal aortic aneurysm in apolipoprotein E-knockout mice via collagen deposition and inflammatory inhibition","volume":"23","author":"Xu","year":"2019","journal-title":"J Cell Mol Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ijcard.2018.04.018","article-title":"Silencing of Non-POU-domain-containing octamer-binding protein stabilizes atherosclerotic plaque in apolipoprotein E -knockout mice via NF-\u03baB signaling pathway","volume":"263","author":"Zhang","year":"2018","journal-title":"Int J Cardiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.3390\/ijms18081758","article-title":"Endocytosis of albumin induces matrix metalloproteinase-9 by activating the ERK signaling pathway in renal tubule epithelial cells","volume":"18","author":"Chen","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"111312","DOI":"10.1016\/j.cellsig.2024.111312","article-title":"Unveiling the bidirectional role of MMP9: A key player in kidney injury","volume":"122","author":"Pang","year":"2024","journal-title":"Cell Signal"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000022278","article-title":"Association of MMP-9 polymorphisms with diabetic nephropathy risk: A protocol for systematic review and meta-analysis","volume":"99","author":"Xie","year":"2020","journal-title":"Med (Baltimore)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2829","article-title":"Comment on american diabetes association. 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