c-Jun N-Terminal Kinase is Upregulated in Patients With Hypospadias

OBJECTIVE To investigate the expression of c-Jun N-terminal kinase (JNK) 1/2 in human hypospadiac tissue compared with that in normal penile tissue. MATERIALS AND METHODS Penile skin tissue specimens obtained at surgery during hypospadias repair or during elective circumcision were divided into 3 groups according to the position of the urethral meatus: children with mild hypospadias (n = 16), severe hypospadias (n = 16), and normal controls (n = 16). The expression of total and phosphorylated JNK1 and JNK2 at the messenger ribonucleic acid and protein levels were assessed using real-time quantitative polymerase chain reaction, immunochemistry, and Western blot analysis. ESULTS JNK1 messenger ribonucleic acid expression and JNK1 and JNK2 phosphorylated protein levels increased significantly in subjects with mild or severe hypospadias compared with the controls (P < .05). JNK2 phosphorylated protein levels increased significantly in those with severe hypospadias compared with those with mild hypospadias (P < .05). Those with hypospadias had increased phosphorylation protein expression of JNK1/2 in the mesenchymal cell layers of the preputial subcutaneous mesenchymal cell layer. CONCLUSION Our findings suggest that JNK upregulation might contribute to the development of hypospadias and might associated with mesenchymal cell migration in the process of external male genitalia defect development. UROLOGY 81: 178-183, 2013. (C) 2013 Elsevier Inc.