Expression of Mafb is down-regulated in the foreskin of children with hypospadias
Expression of Mafb is down-regulated in the foreskin of children with hypospadias
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DOI：
10.1016/j.jpurol.2020.10.006
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发表时间：
2021-03-02
影响因子：
2
通讯作者：
Wei, Guang-hui
中科院分区：
文献类型：
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作者：
Kong, Xiaoyan;Luo, Jin;Wei, Guang-hui
尿道下裂是男性第二常见的先天性畸形。虽然尿道下裂的病因尚不清楚，但通常认为它受到影响尿道发育的遗传和环境内分泌干扰因素的影响，目的探讨转录因子Mafb在尿道下裂组织和正常阴茎组织中的表达差异，探讨其与尿道下裂发生的关系。在重庆医科大学附属儿童医院接受手术修复的尿道下裂患者。诊断为隐睾、双性状态或内分泌异常的患者被排除在研究之外。尿道下裂25例，平均年龄3.5岁，包皮环切术15例，平均年龄5岁。结果尿道下裂患者包皮组织中Mafb mRNA的表达明显低于正常对照组[（1.179 ± 0.1275），（0.6652 ± 0.07506），p < 0.05]。尿道下裂患者的包皮皮下间充质细胞层中Mafb蛋白的表达也降低。尿道下裂患者的Mafb蛋白水平显著低于对照组[（1.932 ± 0.1139），（1.006 ± 0.03312），p < 0.05]。然而，没有这样的差异，发现在Mafb的表达与轻度和重度尿道下裂的主题之间。DiscussionCompared正常包皮，Mafb基因的表达下调在mRNA和蛋白质水平，这是符合我们的RNA-seq测序结果在邻苯二甲酸二乙基己酯（DEHP）诱导的尿道下裂大鼠。本研究首次报道Mafb在尿道下裂患者包皮组织中的异常表达。深入研究Mafb与细胞增殖、细胞凋亡和尿道发育的关系，可能会揭示尿道下裂的发病机制。结论尿道下裂儿童包皮中Mafb基因和蛋白的表达低于正常包皮。我们推测Mafb基因的这种异常表达可能与尿道下裂的发生有关，并且这种异常表达可能影响胚胎期尿道的发育。
BackgroundHypospadias is the second most common congenital malformation in males. Although the aetiology of hypospadias is not clear, it is generally thought to be affected by both genetic and environmental endocrine-disrupting factors that affect the development of the urethra, leading to deformity.ObjectiveTo investigate the difference in expression of the transcription factor Mafb in hypospadias and normal penile tissues and to assess whether it is related to the occurrence of hypospadias.Study designPenile tissue was obtained from children with hypospadias who underwent surgical repair at the Children's Hospital of Chongqing Medical University. Patients diagnosed with undescended testicles, intersex status or endocrine abnormalities were excluded from the study. Twenty-five cases with hypospadias (average 3.5 years old) and 15 cases with circumcisions (as control) (average 5 years old) were included in this study. Real-time quantitative polymerase chain reaction, Immunochemistry and Western blot were used to detect the expression of Mafb.ResultsMafb mRNA expressions in the prepuce of cases with hypospadias was significantly reduced compared with that in the controls [(1.179 +/- 0.1275), (0.6652 +/- 0.07506), p < 0.05)]. Hypospadias cases also showed decreased Mafb protein expression in the preputial subcutaneous mesenchymal cell layer. Mafb protein levels were significantly decreased in those with hypospadias compared with controls [(1.932 +/- 0.1139), (1.006 +/- 0.03312), p < 0.05]. However, no such differences were found in Mafb expression between subjects with mild and severe hypospadias.DiscussionCompared to the normal foreskin, expression of the Mafb gene was down-regulated at both mRNA and protein levels, which was consistent with our RNA-seq sequencing results in Diethylhexyl phthalate (DEHP)-induced hypospadias rats. This study is the first to report abnormal expression of Mafb in the preputial tissue of hypospadias cases. An in-depth study of the relationship between Mafb and cell proliferation, apoptosis, and urethra development may reveal the pathogenesis of hypospadias.ConclusionExpression of the Mafb gene and protein in the foreskin of children with hypospadias is lower than that in normal foreskin. We postulate that such abnormal expression of the Mafb gene may be related to the occurrence of hypospadias and that this abnormal expression may affect the development of the urethra during the embryonic period.