{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:07:50Z","timestamp":1792840070294,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease involves progressive fibrosis and immune dysregulation. Aprotinin, a broad-spectrum serine protease inhibitor, has shown dose-dependent renal effects, but its role in obstructive nephropathy is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A unilateral ureteral obstruction (UUO) mouse model was used to assess aprotinin at 0.5 mg\/day and 1 mg\/day delivered via osmotic pumps for 7 days. Renal injury and fibrosis was evaluated by histology, serum markers, and expression of inflammation- and fibrosis-related genes. Mechanistic insights were obtained through LC-MS\/MS proteomic profiling, functional enrichment analysis, and CIBERSORT-based immune deconvolution. Key proteins, signaling pathways, and immune cell infiltration were validated by Western blotting, immunohistochemistry, and flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Aprotinin at 1 mg\/day significantly reduced tubular injury and interstitial fibrosis, whereas the 0.5 mg\/day dose showed minimal benefit. The higher dose caused mild increases in serum creatinine and blood urea nitrogen. Proteomic analysis identified differentially expressed proteins enriched in immune regulatory pathways. Cathepsin S (CTSS), a protease involved in antigen presentation, was markedly decreased by aprotinin. CIBERSORT revealed reduced follicular helper T cells and partial restoration of na\u00efve CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells following treatment. These changes were further confirmed by flow cytometry. Western blotting and immunohistochemistry confirmed reduced CTSS and CD4 expression, along with decreased CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell infiltration and inhibition of ERK signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Aprotinin attenuates renal fibrosis in UUO in a dose-dependent manner. Its effects are associated with suppression of CTSS, inhibition of ERK signaling, and modulation of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell subsets, and reduced immune cell infiltration. These findings indicate that aprotinin attenuates renal fibrosis through immunomodulatory mechanisms and support further investigation of serine protease inhibitors in immune-mediated kidney injury.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1751652","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:20:00Z","timestamp":1777609200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic insights into aprotinin\u2019s immunomodulatory effects in attenuating renal fibrosis in a unilateral ureteral obstruction model"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Yunnan Provincial Clinical Medical Center for Blood Diseases and Thrombosis Prevention and Treatment, The First People\u2019s Hospital of Yunnan Province, Kunming 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