| First Author | Zhang Z | Year | 2024 |
| Journal | Exp Cell Res | Volume | 436 |
| Issue | 2 | Pages | 113980 |
| PubMed ID | 38401686 | Mgi Jnum | J:346069 |
| Mgi Id | MGI:7613704 | Doi | 10.1016/j.yexcr.2024.113980 |
| Citation | Zhang Z, et al. (2024) Rab25 is involved in hypospadias via the beta1 integrin/EGFR pathway. Exp Cell Res 436(2):113980 |
| abstractText | 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 beta1 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 beta1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice. |
