Role of microRNAs in urethral stricture

Urethral stricture can be defined as the loos of adequate expandability of the urethra, which adversely affects patient health and quality of life. Although it is generally accepted that it occurs with spongiofibrosis and fallowing epithelial damage, the details of these processes are not known precisely. In this study, we aimed to contribute to the explanation of the pathophysiology of urethral stricture. If the pathophysiology can be revealed, new treatment methods can be developed. The treatment of urethral stricture is performed by surgical methods. Non-ivasive and invasive methods can be preferred according to patient characteristics. In some situations, insisting on non-invasive treatment methods may do more harm than good and may negatively affect the success of urethroplasty, which is the definitive treatment. Considering on a patient basis, if early recurrence can be predicted and the etiology can be clarified, early administration of urethroplasty, which is a definitive treatment, may come to the fore without insisting on non-invasive methods. Especially recently, it is seen that various studies have been carried out in the literature on microRNAs (miRNA) in the diagnosis and prognosis of various diseases. For these purposes, we projected to research the role of miRNAs in urethral strictures. Pamukkale University Department of Urology in March 2022 between November 2022, a total of 45 patients who underwent urethroplasty with buccal mucosal graft and anastomotic urethroplasty were included in the study. As the patient group, specimens were taken from the narrow and spogiofibrosis urethral tissue of 30 patients who had urethral stricture that did not develop due to traumatic causes and who underwent urethroplasty with buccal mucosal grafts. As a control group, specimens were taken from healthy urethral tissue spatulized during urethroplasty from 15 patients who had urethral stenosis due to traumatic causes and underwent anastomotic urethroplasty. The urethral tissues taken in both groups were at a level that did not negatively affect the success of surgical treatment. The miRNAs to be investigated from the collected urethral tissues were determined by literature review. miRNAs to be researched were determined as miR-146a-5p, miR-155-5p, miR-142-3p, miR-26b, miR-129-5p, miR-9-5p, miR-29a. Total RNA was isolated from the urethra tissues collected from the individuals participating in the study by means of a commercial kit. The expression levels of the determined miRNA molecules in the obtained RNA samples were investigated by real-time PCR method. 2ΔCt method was used to evaluate miRNA expressions. The fold change values of the miRNAs found by the analyzes were compared statistically between the groups. Mean, standard deviation, median lowest, highest, frequency and ratio values were used in the descriptive statistics of the data. The distribution of variables was measured with the Kolmogorov-Smirnov test. Kruskal-Wallis, Mann-Whitney U test was used in the analysis of quantitative independent data. SPSS 28.0 program was used in the analysis. P<0.05 was considered statistically significant in all analyses. The fold change values of miRNAs were compared between the group of 30 patients with nontraumatic urethral stricture and the control group of 15 patients. In the results, fold change values of miR-29a, miR-155-5p, miR-26b, miR-129-5p, miR-142-3p, miR-146-5p did not differ significantly (P > 0.05). The fold change value of miR-9-5p in the group with urethral stricture was found to be statistically significantly (P < 0.05) lower than the control group. According to our literature review, this is the first study to compare miRNA fold change values between urethral tissue with non-traumatic urethral stricture and control group urethral tissue. In conclusion, we found in our study that miR-9-5p may explain the pathophysiology of urethral stricture. We have demonstrated that miR-9-5p may have protective effects, but the clinical findings of patients appear before the completion of the pathophysiological process in urethral fibrosis. Keywords: Urethral stricture, miRNA, fibrosis, spongiofibrosis, urethroplasty