Triamcinolone acetonide combined with 5-fluorouracil suppresses urethral scar fibroblasts autophagy and fibrosis by increasing miR-192-5p expression.

Urethral stricture is one of the common diseases in urology. It can lead to obstructive voiding dysfunction and may cause long-term damage to the entire urinary tract. Here, we investigated the effect of combined use of 5-fluorouracil (5-FU) and triamcinolone acetonide (TA) in improving urethral stricture. We established urethral stricture in vivo and in vitro model. The role of TA combined with 5-FU treatment in scar tissue and fibroblast cells were examined by RT-PCR, Western blot and immunohistochemical methods. The function of miRNA in improving urethral stricture by TA combined with 5-FU treatment were further investigated. We found that TA combined with 5-FU treatment obviously prevent urethral fibrosis in vivo as well as in vitro. MiR-192-5p level was downregulated in urethral stricture tissue and urethral tissue fibroblast, TA combined with 5-FU treatment rescue the expression of miR-192-5p. The improvement of urethral fibrosis by TA combined with 5-FU treatment was blocked by miR-192-5p inhibitor. miR-192-5p mediated the improvement of urethral scar by triamcinolone acetonide combined with 5-FU by directly targeting ATG7, which is marker gene of autophagy. Our data demonstrated that TA combined with 5-FU suppresses urethral scar fibroblasts autophagy and fibrosis by increasing miR-192-5p expression, thus offering a new strategies and target for Urethral stricture.