Rab25 通过β1 整合素/EGFR 通路参与尿道下裂的发生。
Rab25 is involved in hypospadias via the β1 integrin/EGFR pathway.
机构信息
Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China.
Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Program for Youth Innovation in Future Medicine, Chongqing Medical University, Chongqing, 400014, PR China.
出版信息
Exp Cell Res. 2024 Mar 15;436(2):113980. doi: 10.1016/j.yexcr.2024.113980. Epub 2024 Feb 23.
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 mice.
RESULTS
An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25 mice. We demonstrated that Rab25 mediated hypospadias through the β1 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 β1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice.
背景
尿道下裂是一种常见的阴茎先天性畸形。涉及尿道发育的关键基因异常调控导致尿道下裂。我们使用 Rab25 小鼠和经慢病毒转染的包皮成纤维细胞在体内和体外研究 Rab25 在尿道下裂中的作用。
方法
使用分子生物学方法（Western blot、PCR、免疫组织化学等）确认组织样本和包皮成纤维细胞中各种分子的表达水平。使用扫描电子显微镜（SEM）观察妊娠第 18.5 天的野生型（WT）和 Rab25 小鼠的生殖器嵴（GT）的外部形态。
结果
在 GD18.5 Rab25 小鼠中观察到扩大的远端裂隙和 V 形尿道开口。我们证明 Rab25 通过β1 整合素/EGFR 途径介导尿道下裂。此外，沉默 Rab25 抑制包皮成纤维细胞的增殖和迁移，并促进细胞凋亡；Ki-67 和 TUNEL 阳性细胞主要集中在尿道缝附近。
结论
这些发现表明，Rab25 通过激活β1 整合素/EGFR 途径在尿道下裂中发挥重要作用，Rab25 是 GD18.5 雄性胎鼠尿道缝形成的关键介质。
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