Kong Xiaoyan, Liu Zhenmin, Long Chunlan, Shen Lianju, Liu Xing, Wei Guanghui
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.
Andrologia. 2022 Jul;54(6):e14411. doi: 10.1111/and.14411. Epub 2022 Feb 27.
Mafb plays a significant role in the development and differentiation of various organs, tissues and cells. Nevertheless, its role in the control of external genital cell proliferation and function in the mechanism of hypospadias remains unknown. In this study, the expression of Mafb in foreskin fibroblasts was inhibited by siRNA. The Cell Count Kit-8 (CCK-8) assay showed cell proliferation increased after transfection, and the number of cells entered the S phase significantly increased via flow cytometry. Both mRNA and protein levels of cyclin E, cyclin-dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) were significantly upregulated in the siRNA group. Meanwhile, twenty-five prepuce tissue samples were collected from hypospadias repair surgery. These samples were divided into two groups: the severe and mild groups. Normal prepuce tissue specimens were obtained during circumcision as the normal control. The upregulated expression of cyclin E, CDK2 and PCNA and downregulated Mafb expression were observed in the hypospadias group. This study reveals for the first time that the reduction in Mafb promotes the foreskin fibroblast proliferation. Thus, downregulated Mafb expression may cause hypospadias by upregulating CDK2, cyclin E and PCNA. These findings can shed new light on the embryonic development of the urethra.
Mafb在多种器官、组织和细胞的发育与分化中发挥着重要作用。然而，其在控制外生殖器细胞增殖以及尿道下裂机制中的功能仍不清楚。在本研究中，小干扰RNA（siRNA）抑制了包皮成纤维细胞中Mafb的表达。细胞计数试剂盒-8（CCK-8）检测显示转染后细胞增殖增加，通过流式细胞术检测发现进入S期的细胞数量显著增加。在siRNA组中，细胞周期蛋白E、细胞周期蛋白依赖性激酶2（CDK2）和增殖细胞核抗原（PCNA）的mRNA和蛋白水平均显著上调。同时，收集了25例尿道下裂修复手术中的包皮组织样本。这些样本分为两组：重度组和轻度组。在包皮环切术中获取正常包皮组织标本作为正常对照。在尿道下裂组中观察到细胞周期蛋白E、CDK2和PCNA的表达上调以及Mafb表达下调。本研究首次揭示Mafb表达降低促进包皮成纤维细胞增殖。因此，Mafb表达下调可能通过上调CDK2、细胞周期蛋白E和PCNA导致尿道下裂。这些发现可为尿道的胚胎发育提供新的线索。
