{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:49:59Z","timestamp":1792810199338,"version":"4.5.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"1","funder":[{"name":"Thompson Family Foundation"},{"DOI":"10.13039\/100011087","name":"Society of Interventional Radiology","doi-asserted-by":"crossref","award":["Ernest Ring Grant"],"award-info":[{"award-number":["Ernest Ring Grant"]}],"id":[{"id":"10.13039\/100011087","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["U54CA137788\/ U54CA132378"],"award-info":[{"award-number":["U54CA137788\/ U54CA132378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Frederick J and Theresa Down Wallace Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:p>\n                    Iatrogenic injury to the healthy ureter during ureteroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -mediated scar formation is considered to underlie ureteral stricture, but the cellular sources of this cytokine and the sequelae preceding iatrogenic stricture formation are unknown. Using a swine model of ureteral injury with irreversible electroporation (IRE), we evaluated the cellular sources of TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    and scar formation at the site of injury and examined in vitro whether the effects of TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    could be attenuated by pirfenidone. We observed that proliferation and \u03b1-smooth muscle actin expression by fibroblasts were restricted to injured tissue and coincided with proliferation of macrophages. Collagen deposition and scarring of the ureter were associated with increased TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    expression in both fibroblasts and macrophages. Using in vitro experiments, we demonstrated that macrophages stimulated by cells that were killed with IRE, but not LPS, secreted TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    , consistent with a wound healing phenotype. Furthermore, using 3T3 fibroblasts, we demonstrated that stimulation with paracrine TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    is necessary and sufficient to promote differentiation of fibroblasts and increase collagen secretion. In vitro, we also showed that treatment with pirfenidone, which modulates TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    activity, limits proliferation and TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    secretion in macrophages and scar formation-related activity by fibroblasts. In conclusion, we identified wound healing-related macrophages to be an important source of TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    in the injured ureter, which may be a paracrine source of TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    driving scar formation by fibroblasts, resulting in stricture formation.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00260.2018","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T07:53:10Z","timestamp":1556092390000},"page":"F52-F64","source":"Crossref","is-referenced-by-count":124,"title":["Macrophage-secreted TGF-\u03b2\n                    <sub>1<\/sub>\n                    contributes to fibroblast activation and ureteral stricture after ablation injury"],"prefix":"10.1152","volume":"317","author":[{"given":"Eisuke","family":"Ueshima","sequence":"first","affiliation":[{"name":"Department of Radiology, Interventional Radiology Service, 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