Eosinophilic inflammation that begins in the juvenile stage causes hydronephrosis and urothelial cancer in mutant mice

Obstructive hydronephrosis is caused by various factors such as chronic inflammation and tumors. Eosinophils and chitinase-like proteins (CLPs) are involved in the pathogenesis of hydronephrosis in mice; however, the specific mechanisms remain unknown. In this study, we morphologically analyzed a novel mouse model of obstructive hydronephrosis from onset to progression to clarify the effects of eosinophils and CLP on the development of hydronephrosis and tumorigenesis. The primary change was slight eosinophil infiltration of the ureteropelvic junction, even at 1 week of age, followed by a significant increase in CLP expression in the urothelium at 5 weeks of age, which led to proliferation of the urothelium. At 8 weeks of age, polyps with eosinophilic inflammation and urothelial hyperplasia expressing high levels of CLP formed at the ureteropelvic junction, leading to hydronephrosis. At 60 weeks of age, all mice with hydronephrosis exhibited chronic eosinophilic inflammation and adenomas that progressed to adenocarcinomas with high CLP expression. In summary, inflammation and epithelial proliferation at the ureteropelvic junction began with a single infiltration of eosinophils at the juvenile stage in mice. Eosinophilic inflammation is associated with the development of hydronephrosis and urothelial hyperplasia, which may progress to urothelial adenocarcinoma due to increased CLP expression.