Expression of Rab25 is down-regulated in the foreskin of children with hypospadias

作者全名："Zhang, Qiang; Zhang, Zhicheng; He, Xueyu; Liu, Zhenmin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing"

作者地址："[Zhang, Qiang; Zhang, Zhicheng; He, Xueyu; Liu, Zhenmin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat,Minist Educ,Key Lab Child, Chongqing 400014, Peoples R China; [Zhang, Qiang; Zhang, Zhicheng; He, Xueyu; Liu, Zhenmin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Zhang, Qiang; Zhang, Zhicheng; He, Xueyu; Liu, Zhenmin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing] Chongqing Med Univ, Pediat Res Inst, Childrens Hosp, Chongqing 400014, Peoples R China; [Liu, Xing] Chongqing Med Univ, Program Youth Innovat Future Med, Chongqing 400014, Peoples R China"

通信作者："Liu, X (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China."

来源：JOURNAL OF PEDIATRIC UROLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001085205600001

JCR分区：Q2

影响因子：2

年份：2023

卷号：19

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：Hypospadias; Rab25; b1-integrin; Epidermal growth factor receptor; Epithelial-mesenchymal transition

摘要："BackgroundHypospadias, a congenital malformation of the penis, is one of the newborns' most common developmental defects. The incidence of hypospadias is increasing yearly, and its pathogenesis is closely related to genetic susceptibility and environmental exposure to endocrine disruptors. Exploring the hypospadias' key molecular regulatory mechanism is crucial to reducing its incidence.ObjectiveTo examine the differential expression of Rab25 in hypospadias and normal penile tissue and to identify whether it is a candidate gene for exploring the mechanism of hypospadias.Study designThis study included 18 children aged 1-6 years undergoing hypospadias repair surgery at the Children's Hospital of Chongqing Medical University, and foreskin samples were collected. Children diagnosed with cryptorchidism, intersex status, or endocrine abnormalities were excluded from this study. Another 18 children aged 3-8 years with phimosis were included in the control group. The specimens were used for immunohistochemistry, western blot-ting, immunofluorescence, and polymerase chain reaction to assess the expression of Rab25.ResultsRab25 protein expression was lower in the hypospadias group than in the control group [ (2.101 +/- 0.1845), (0.7506 +/- 0.1779), p = 0.0008 < 0.05). The hypospadias group showed decreased expression of Rab25 protein in the epithelial cell layer. Rab25 mRNA levels were downregulated in the foreskin of children with hypospadias compared with controls [(1.697 +/- 0.2005), (0.7687 +/- 0.2130), p = 0.0053 < 0.05)].DiscussionRab25 mRNA and protein expressions in the hypospadias group were significantly down-regulated compared with the control group. This was consistent with the results of single-cell sequencing of fetal mice reproductive nodules at 15.5 days of gestation (Zhang Z, Liu Z, Zhang Q, et al., unpublished observations). Our study represents the first report of abnormal Rab25 expression in the foreskin tissue of patients with hypospadias. More detailed research on the relationship between Rab25 and urethral development could be conducted to reveal the molecular mechanism of hypospadias. Conclusion The expression of Rab25 in foreskin tissue was lower in the hypospadias group than in the control group. Rab25 is involved in the formation of the urethral seam and the occurrence of hypospadias. The po-tential mechanism by which Rab25 affects the canalization of the urethral plate needs to be further investigated."

基金机构：Department of Urology of Children's Hospital of Chongqing Medical University; National Natural Science Foundation of China

基金资助正文：We would acknowledge the support of the Department of Urology of Children's Hospital of Chongqing Medical University and the financial support of the National Natural Science Foundation of China.