2. Academic Validation
  3. Rab25 is involved in hypospadias via the β1 integrin/EGFR pathway

Rab25 is involved in hypospadias via the β1 integrin/EGFR pathway

  • Exp Cell Res. 2024 Mar 15;436(2):113980. doi: 10.1016/j.yexcr.2024.113980.
Zhicheng Zhang 1,  Qiang Zhang 1,  Zhenmin Liu 1,  Chong Wang 1,  Hongsong Chen 1,  Xingguo Luo 1,  Lianju Shen 1,  Chunlan Long 1,  Guanghui Wei 1,  Xing Liu 2
Affiliations

Affiliations

  • 1 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.
  • 2 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. Electronic address: liux@hospital.cqmu.edu.cn.
PMID: 38401686 DOI: 10.1016/j.yexcr.2024.113980
Abstract

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.

Keywords

EGFR; Genital tubercle; Hypospadias; Rab25; β1 integrin.

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