{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:50:40Z","timestamp":1773733840285,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"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>Ureteral stricture (US), characterized by fibrotic remodeling of the ureteral wall, represents an obstructive urological disorder with incompletely characterized pathophysiological mechanisms. This study integrates single-cell RNA sequencing (scRNA-seq) with immunohistochemical validation in human tissues to investigate the molecular and cellular mechanisms underlying US pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Specimens of US (n = 7) and normal ureters (n = 8) were collected from patients prospectively. Single-cell RNA sequencing was performed to dissect the transcriptomic landscape of US, with subsequent immunohistochemical and immunofluorescence staining employed to validate key molecular and cellular findings at the protein level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In US tissues, we identified significant downregulation of urothelial cell-specific gene signatures, accompanied by attenuated intercellular crosstalk between urothelial cells and fibroblasts. The urothelial cells exhibited reduced expression of reactive oxygen species (ROS)-associated functional clusters, with ANXA1 gene demonstrating particularly pronounced downregulation compared to control samples. Additionally, fibroblasts in US tissues displayed decreased expression of the THBS1 subtype and significant reduction in fibroblast-specific FPR2 receptor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings establish that impaired urothelial cell function and disrupted urothelial-fibroblast communication are critically associated with or contributing to fibrotic remodeling in US. Specifically, control urothelial cells secrete ANXA1 as a ligand to interact with the fibroblast-expressed FPR2 receptor, maintaining fibroblast homeostasis. Clinically, these insights provide novel theoretical foundations for US prevention and highlight potential therapeutic targets for antifibrotic intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1786116","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:26:19Z","timestamp":1773725179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Attenuated crosstalk between urothelium and fibroblasts promotes ureteral stricture development"],"prefix":"10.3389","volume":"17","author":[{"given":"Rongchang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Urology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of 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