Zhang J, Zhang Z B, Gao H, Zhang D, Wang W L
Department of Paediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
J Int Med Res. 2009 Nov-Dec;37(6):1842-50. doi: 10.1177/147323000903700620.
The sonic hedgehog homologue (SHH)/bone morphogenetic protein 4 (BMP4) signalling pathway is involved in the morphogenesis of many organ systems. This study was designed to investigate the expression of SHH/BMP4 pathway components in human anorectal malformations (ARMs) and the relationship between expression of their genes and the occurrence of ARMs. Expression of SHH, GLI family zinc finger 2 (GLI2) and BMP4 mRNA in the posterior wall of the terminal rectum in 40 patients with ARMs (15 high-type and 25 low-type) and 10 normal controls was assessed by reverse transcription-polymerase chain reaction. Levels of SHH, GLI2 and BMP4 proteins were assessed by immunohistochemistry and Western blotting. The expressions of SHH, GLI2 and BMP4 were significantly lower in patients with high-type compared with those with low-type anomalies and controls. Patients with low-type ARMs differed from controls only in the expression of GLI2 mRNA. It is concluded that down-regulation of the SHH/BMP4 signalling pathway may be related to the occurrence of high-type ARMs, but the mechanism responsible for low-type ARMs remains unclear.
音猬因子同源物（SHH）/骨形态发生蛋白4（BMP4）信号通路参与了许多器官系统的形态发生。本研究旨在调查SHH/BMP4通路成分在人类肛门直肠畸形（ARM）中的表达情况以及它们基因的表达与ARM发生之间的关系。通过逆转录-聚合酶链反应评估了40例ARM患者（15例高位型和25例低位型）和10例正常对照者终末直肠后壁中SHH、GLI家族锌指蛋白2（GLI2）和BMP4 mRNA的表达。通过免疫组织化学和蛋白质印迹法评估SHH、GLI2和BMP4蛋白的水平。与低位型畸形患者和对照者相比，高位型患者中SHH、GLI2和BMP4的表达显著降低。低位型ARM患者与对照者仅在GLI2 mRNA表达上存在差异。结论是，SHH/BMP4信号通路的下调可能与高位型ARM的发生有关，但低位型ARM的发病机制仍不清楚。
