{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:21Z","timestamp":1785411501283,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007086","name":"Selcuk University","doi-asserted-by":"publisher","award":["25122011"],"award-info":[{"award-number":["25122011"]}],"id":[{"id":"10.13039\/501100007086","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25122011"],"award-info":[{"award-number":["25122011"]}],"id":[{"id":"https:\/\/ror.org\/045hgzm75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Silicosis is a progressive occupational lung disease characterized by persistent inflammation and irreversible pulmonary fibrosis. Reliable circulating biomarkers for the early detection of fibrotic remodeling and monitoring of disease progression remain limited. Prolidase, a key enzyme involved in collagen turnover and extracellular matrix remodeling, has emerged as a potential biomarker in fibrotic disorders. Therefore, this study aimed to evaluate the potential role of serum prolidase as a biomarker for fibrotic remodeling and treatment monitoring in an experimental rat model of silicosis. Methods: Male Wistar rats were divided into three groups: control, silicosis, and silicosis plus nintedanib. Silicosis was induced by intratracheal crystalline silica instillation. Nintedanib was administered by gastric gavage at 50 mg\/kg\/day from day 10 to day 30. Lung tissues were evaluated histopathologically using hematoxylin and eosin and Masson\u2019s trichrome staining. Serum prolidase, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-\u03b2) levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Histopathological injury scores were significantly increased in the silicosis group and were attenuated by nintedanib treatment. Serum prolidase levels were significantly higher in both silica-exposed groups than in controls (p = 0.017), but did not differ significantly between untreated and nintedanib-treated animals. TGF-\u03b2, FGF-2, and PDGF levels were also significantly elevated following silica exposure. Serum prolidase showed a strong positive correlation with TGF-\u03b2 (r = 0.69, p &lt; 0.001). ROC analysis demonstrated good diagnostic performance for prolidase (AUC = 0.877), while the combined Prolidase + TGF-\u03b2 model further improved discrimination (AUC = 0.969). The internally validated multivariable biomarker panel maintained high diagnostic accuracy after leave-one-out cross-validation (LOOCV) (AUC = 0.892). Conclusions: Serum prolidase may serve as a potential circulating biomarker of silica-associated fibrotic remodeling. Although nintedanib improved histopathological lung injury, persistently elevated prolidase levels suggest ongoing extracellular matrix remodeling rather than short-term treatment response. Further longitudinal experimental and clinical studies are warranted to validate its diagnostic and prognostic utility.<\/jats:p>","DOI":"10.3390\/jcm15145621","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"5621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Serum Prolidase as a Biomarker and the Effects of Nintedanib in an Experimental Rat Model of Silicosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5699-8782","authenticated-orcid":false,"given":"Ezgi Nur","family":"Ayd\u0131n","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-2250","authenticated-orcid":false,"given":"Dilek","family":"Erg\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-9188","authenticated-orcid":false,"given":"Recai","family":"Erg\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2654-7621","authenticated-orcid":false,"given":"Bahad\u0131r","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1297-426X","authenticated-orcid":false,"given":"Mehmet Burak","family":"Ate\u015f","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5128-3420","authenticated-orcid":false,"given":"Selman Turgut","family":"Ko\u00e7ak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-5307","authenticated-orcid":false,"given":"Menendi Merve Sava\u015f","family":"G\u00fcvendik","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Sel\u00e7uk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12995-025-00455-8","article-title":"A review of silicosis and other silica-related diseases in the engineered stone countertop processing industry","volume":"20","author":"Fazio","year":"2025","journal-title":"J. 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