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

Li, Ming-yong; Qiu, Lin; Lin, Tao; He, Dalin; Hua, Yi; Yuan, Xi; Liu, Xing; Wei, Guanghui

doi:10.1016/j.urology.2012.09.010

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…The clinical characteristics of hypospadias are significantly heterogeneous and complex (17). According to the anatomical location of urethral meatus at the point of medial-ventral side of the penis after chordee has been released, the hypospadias is classified as anterior hypospadias (glanular and subcoronal), middle hypospadias (from distal penile to midshaft) and posterior hypospadias (proximal penile, penoscrotal, scrotal and perineal) (18).…”

Section: Discussionmentioning

confidence: 99%

“…JNK has been proposed to be associated with mesenchymal cell migration in the process of external male genitalia defect development. Li et al reported that JNK protein levels were significantly increased in mild or severe hypospadias subjects compared to the controls, and hypospadias group had increased phosphorylation JNK1 and JNK2 protein expression in the mesenchymal cell layers of the preputial subcutaneous mesenchymal cell layer (17).…”

Section: Discussionmentioning

confidence: 99%

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Quantitative proteomics reveals specific protein regulation of severe hypospadias

Zhu¹,

Fu²,

Hu³

et al. 2022

Transl Androl Urol

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Background: The etiological mechanism of hypospadias is multifactorial and may be heterogeneous by severity. To date, very limited analyses on proteome in hypospadias have been conducted, and there are still no severe hypospadias proteomics analyses.Methods: In our study, tandem mass tag (TMT)-based quantitative proteomics was performed, exploring the clinical samples from hypospadias patients and healthy donators, in order to identify distinctly expressed proteins for severe hypospadias. To further uncover the mechanistic links in these complex proteomics data, we performed several core ingenuity pathway analyses (IPA) to predict, based on these observed different expression of proteins (DEPs).Results: Compared with the unaffected controls, 299 proteins were found to be down-regulated and 176 proteins up-regulated in severe hypospadias foreskin tissues. Functional annotation revealed that these DEPs were mainly in the extracellular space and were associated with complement activation and coagulation cascades. Similarly, the IPA core analysis revealed enriched pathways of the acute phase response signaling and complement system, demonstrating that by mediating their targeted, differentiated expressed proteins

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics reveals specific protein regulation of severe hypospadias

Zhu¹,

Fu²,

Hu³

et al. 2022

Transl Androl Urol

View full text Add to dashboard Cite

show abstract

“…Hypospadias is probably a multifactorial disorder; maternal exposure to estrogenic compounds interfering with the production or action of fetal androgens and disrupted gene expression have been related to this defect.…”

Section: Discussionmentioning

confidence: 99%

Split Median Raphe: Case Series and Brief Literature Review

Valerio

Cutrone

2014

Pediatric Dermatology

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We describe three cases of split median raphe of the penis (SMR) from our hospital newborn records from 2004 to 2013. One case was associated with median raphe cyst, one with skin hypochromia, and one with a scar-like aspect of the region of interest. SMR is thought to be the result of defective fusion of ectodermal tissue in the urethra and scrotum area or of defective growth of the perineal mesoderm around the urethra during gestation. Although SMR associated with other major penile congenital defects (epispadias, hypospadias, penile torsion, bifid scrotum, chordee) is common, isolated SMR is probably an underdiagnosed (although not rare) malformative condition. Recognizing SMR in a newborn may be of educational value to neonatologists because it leads to the search for and exclusion of the above-mentioned pathologic conditions.

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“…At the protein level, findings also differ between hypospadias severities. Protein expression level of c-Jun N-terminal kinase 2 (JNK2), involved in cell migration, was found significantly increased in penile skin tissue from boys with severe hypospadias in comparison to boys with mild hypospadias (13). In addition, AR protein expression was found at higher levels in preputial tissue from subjects with severe hypospadias than those with mild hypospadias and control subjects (14).…”

Section: Introductionmentioning

confidence: 98%

Severity-Dependent Profile of the Metabolome in Hypospadias

et al. 2020

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Background & Objective: Hypospadias, characterized by the displacement of the opening of the urethra at any point in the medial-ventral side of the penis, is classified upon severity as mild (Type I) and severe (Type II and Type III) hypospadias. Hypospadias' etiology is idiopathic in the majority of cases, and underlying causes seem of multifactorial origin. Studies regarding genetic variants support this notion. It is unknown whether downstream gene products fit this profile. This study evaluated the metabolome of hypospadias by using the emerging technology of metabolomics in the search for distinct cellular processes associated with hypospadias' etiology according to the severity of this congenital urogenital condition. Methods: Foreskin samples were collected during urethroplasty from boys with Type I, II, and III hypospadias or undergoing elective circumcision (N = 28) between 5 and 28 months of age. Samples were processed and submitted to gas chromatography-mass spectrometry (GC/MS). MetaboloAnalyst (http://www.metaboanalyst.ca/) online platform was used for bioinformatic analyses. Results: Thirty-five metabolites across experimental groups were identified by GC/MS. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed that the metabolome of Type II and Type III hypospadias patients differs from the metabolome of Type I hypospadias and control patients. Of those 35, 10 amino acids were found in significantly low concentrations in severe hypospadias: aspartate, glutamate, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, and tyrosine. A high concentration of the amino acid lysine was detected in mild hypospadias. Conclusions: The observed downregulation of specific amino acids in severe hypospadias provides alternative routes for future research aiming to identify disrupted networks and pathways while considering the severity of hypospadias.

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

Cited by 6 publications

References 29 publications

Quantitative proteomics reveals specific protein regulation of severe hypospadias

Quantitative proteomics reveals specific protein regulation of severe hypospadias

Split Median Raphe: Case Series and Brief Literature Review

Severity-Dependent Profile of the Metabolome in Hypospadias

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