Expression of NGF, MCP-1, uroplakin III, and NOS in bladder urothelium after partial urethral obstruction in rats

Abstract

Although several cytokines, chemokines, and growth factors have been suggested to play a role in the development of bladder fibrosis and functional changes, the mechanisms that are effective in the pathogenesis of partial bladder outlet obstruction (pBOO)-induced bladder fibrosis are not well understood. We investigated the expressions of nerve growth factor (NGF), monocyte chemoattractant protein-1 (MCP-1), uroplakin III (URPIII), inducible nitric oxide synthase (iNOS), and endothelial NOS (eNOS) that may be involved in fibrosis in rats with partial urethral obstruction for 1, 2 and 3 weeks, and the changes in the associated ischemic and inflammatory processes. After 1, 2, and 3 weeks of pBOO, blood samples were collected for assessment of renal function from the rats under anesthesia. The bladders were dissected for the tissue antioxidant enzyme activities and lipid peroxidation, including malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS) and total oxidant status (TOS). The immunohistochemical studies were performed. Histopathologically, the number of urothelial layers was calculated and the thickness of the detrusor smooth muscle and lamina propria were quantitatively measured. Additionally, the edema and congestion in the submucosa were evaluated. Twenty-eight male Sprague-Dawley rats were used in this study. Three separate experimental groups of pBOO (1 week [n=7], 2 weeks [n=7], and 3 weeks [n=7]) were created, with an additional sham-operated control group (n=7). The MDA levels increased in pBOO groups. The SOD values were decreased in the pBOO group for 1 week, and higher in the 3-week pBOO group. The TAS levels were increased in the 3 week pBOO group. The TOS levels increased in the pBOO groups. The number of urothelial layers was decreased in pBOO groups. The lamina propria, the smooth muscle thickness, edema and congestion were increase in the 1 and 2 week pBOO groups. The NGF and MCP-1 expression was increased in the 1-week and 2-week pBOO groups. The expression of URPIII in the epithelium gradually increased in the pBOO groups. In the pBOO groups, iNOS expression in the epithelium cells was significantly elevated. However, the eNOS expression was also significantly increased in the 2 week pBOO group. Our study shows that overexpression of immunohistochemical parameters together with the negative effects of ischemic and inflammatory processes that subjected to pBOO for 1, 2 and 3 weeks may play a potential role in detrusor fibrosis in the rat bladders induced by pBOO. However, understanding of the immunohistochemical parameters investigated in this experimental study is limited, and further studies targeting their relationship to pBOO could help us develop new strategies.