{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:10:42Z","timestamp":1774948242818,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis\/chronic pelvic pain syndrome (CP\/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4\u2010methylumbelliferone (4\u2010MU) (200\u2009mg\/kg\/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co\u2010expression network analysis (WGCNA) to identify co\u2010expressed gene modules and hub\u2010gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HA was significantly more highly expressed in CP\/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4\u2010MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co\u2010expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4\u2010MU\u2010treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4\u2010MU treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that HA is elevated in patients with CP\/CPPS compared with healthy controls and that targeting HA through 4\u2010MU suppresses the activity of the cell cycle\u2010related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24205","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T17:13:45Z","timestamp":1627492425000},"page":"1078-1090","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["4\u2010Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-3013","authenticated-orcid":false,"given":"Jing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, and Anhui Province Key Laboratory of Genitourinary Diseases Anhui Medical University Hefei Anhui 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