Macrophage-secreted TGF-beta_1 contributes to fibroblast activation and ureteral stricture after ablation injury

摘要

Iatrogenic injury to the healthy ureter during uret-eroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-Pi-mcdiated 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 electroporalion (IRE), we evaluated the cellular sources of TGF-beta and scar formation at the site of injury and examined in vitro whether the effects of TGF-beta_1 could be attenuated by pirfenidone. We observed that proliferation and ot-smooth muscle actin expression by fibroblasts were restricted to injured tissue and coincided with proliferation of macrophages.