Zhou Weidong, Yu Qingsong, Ma Junjie, Xu Chengdang, Wu Denglong, Li Chao
Department of Urology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
Am J Transl Res. 2021 Jun 15;13(6):5956-5968. eCollection 2021.
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 and 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 as well as . 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.
尿道狭窄是泌尿外科的常见疾病之一。它可导致排尿梗阻性功能障碍，并可能对整个尿路造成长期损害。在此，我们研究了5-氟尿嘧啶（5-FU）和曲安奈德（TA）联合使用对改善尿道狭窄的作用。我们建立了尿道狭窄模型。通过逆转录-聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫组织化学方法检测TA联合5-FU治疗在瘢痕组织和成纤维细胞中的作用。进一步研究了微小RNA（miRNA）在TA联合5-FU治疗改善尿道狭窄中的作用。我们发现TA联合5-FU治疗明显预防尿道纤维化。尿道狭窄组织和尿道组织成纤维细胞中miR-192-5p水平下调，TA联合5-FU治疗可挽救miR-192-5p的表达。miR-192-5p抑制剂可阻断TA联合5-FU治疗对尿道纤维化的改善作用。miR-192-5p通过直接靶向自噬标记基因ATG7介导曲安奈德联合5-FU对尿道瘢痕的改善作用。我们的数据表明，TA联合5-FU通过增加miR-192-5p表达抑制尿道瘢痕成纤维细胞自噬和纤维化，从而为尿道狭窄提供了新的策略和靶点。
