Rab25 is involved in hypospadias via the 81 integrin/EGFR pathway

作者全名：Zhang, Zhicheng; Zhang, Qiang; Liu, Zhenmin; Wang, Chong; Chen, Hongsong; Luo, Xingguo; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing

作者地址：[Zhang, Zhicheng; Zhang, Qiang; Liu, Zhenmin; Wang, Chong; Chen, Hongsong; Luo, Xingguo; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing] Chongqing Med Univ, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat, Natl Clin Res Ctr Child Hlth & Disorders,Minist Ed, Chongqing 400014, Peoples R China; [Zhang, Zhicheng; Zhang, Qiang; Liu, Zhenmin; Wang, Chong; Chen, Hongsong; Luo, Xingguo; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Liu, Xing] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China; [Zhang, Zhicheng; Zhang, Qiang; Liu, Zhenmin; Wang, Chong; Chen, Hongsong; Luo, Xingguo; 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, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China.

来源：EXPERIMENTAL CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001221928200001

JCR分区：Q2

影响因子：3.3

年份：2024

卷号：436

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Hypospadias; Rab25; 81 integrin; EGFR; Genital tubercle

摘要：Background: Hypospadias is a common congenital abnormality of the penile. Abnormal regulation of critical genes involved in urethral development leads to hypospadias. We used the Rab25 -/- mice and foreskin fibroblasts transfected with lentivirus in vitro and in vivo to investigate the role of Rab25 in hypospadias. Methods: The expression levels of various molecules in tissue samples and foreskin fibroblasts were confirmed using molecular biology methods (western blotting, PCR, immunohistochemistry, etc.). A scanning electron microscope (SEM) was used to visualize the external morphology of genital tubercles (GTs) of gestation day (GD) 18.5 male wild -type (WT) and Rab25 <inverted exclamation> / <inverted exclamation> mice. Results: An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25 <inverted exclamation> / <inverted exclamation> mice. We demonstrated that Rab25 mediated hypospadias through the 8 1 integrin/EGFR pathway. In addition, silencing Rab25 inhibited cell proliferation and migration and promoted apoptosis in the foreskin fibroblasts; Ki-67- and TUNEL-positive cells were mainly concentrated near the urethral seam. Conclusion: These findings suggest that Rab25 plays an essential role in hypospadias by activation of 8 1 integrin/ EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice.

基金机构：National Natural Science Foundation of China [81970571]; Natural Science Foundation of Chongqing Science and Technology Commission [CSTB2022NSCQ-MSX1001]

基金资助正文：This study was funded by [National Natural Science Foundation of China] (Grant numbers [81970571] ) and [Natural Science Foundation of Chongqing Science and Technology Commission] (Grant numbers [CSTB2022NSCQ-MSX1001] ) .