Expression of Growth Associated Protein-43 in Intestinal Tissues of Patients with Hirschsprung Disease_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HUANGFa-xin ^1,2 ,  LIULei ¹ , WANGJian-yao ¹ , XUJin-yong ¹

1. Department of General Surgery, Shen zhen Childrens'Hospital, Shenzhen 518038, Guangdong Province, China;
2. Clinical College, Zunyi Medical College, Zhuhai 519090, Guangdong Province, China;

Corresponding author：

LIULei, Email: liulei3322@aliyun.com

Keywords：

Growth associated protein-43; Hirschsprung disease; Enteric nervous system; Immunohistochemistry; Real-time RCR

DOI：

10.7507/1007-9424.20150090

Video：

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Objective To explore the expression of growth associated protein-43 (GAP-43) in spasm segment and expansion segment of hirschsprung disease (HD), and to explore the pathogenesis of HD. Methods The expression of GAP-43 in 30 patients with HD who underwent surgical resection for absence of enteric plexuses from Jan. 2012 to Jun. 2013 in Shen zhen Children's Hospital were analyzed by using immunohistochemistry method and real-time PCR method. Aganglionic tissues of all patients were included as spasm group, and ganglionic tissues of the same patients were served as expansion group. Then comparison of the expression levels of GAP-43 mRNA and its protein between 2 groups was performed. Results of real-time RCR showed that the expression level of GAP-43 mRNA in expansion group was higher than that of spasm group (0.119 0 vs. 0.052 8, P<0.05). Immunohistochemistry results showed that GAP-43 protein expressed both in the myenteric plexus and ganglionic plexus of submucos in all patients, but lighter in spasm group. Compared with ganglionic plexus of circular muscle layer and longitudinal muscle layer/ganglionic plexus of submucosa in expansion group, the average optical density values at corresponding sites of intestinal tissues in spasm group were both lower (P<0.05). Conclusion Expression of GAP-43 protein is lower in spastic intestinal tissue of patients with HD, which suggests that down-regulation of GAP-43 protein may be a risk factor for HD.

Citation： HUANGFa-xin, LIULei, WANGJian-yao, XUJin-yong. Expression of Growth Associated Protein-43 in Intestinal Tissues of Patients with Hirschsprung Disease. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(3): 339-342. doi: 10.7507/1007-9424.20150090 Copy

1.	Mckeown SJ, Stamp L, Hao MM, et al. Hirschsprung disease:a developmental disorder of the enteric nervous system. Wiley Interdiscip Rev Dev Biol, 2013, 2(1):113-129.
2.	黎明, 肖雅玲. 120例先天性巨结肠发病危险因素分析及外科治疗. 中国医药导刊, 2013, 15(2): 259-261.
3.	刘鹏飞, 秦克旺, 吴坤河, 等. HAND2蛋白在先天性巨结肠肠壁肌间神经丛中的表达及意义. 广东医学, 2013, 34(10):1513-1515.
4.	覃宇冰. HuD蛋白在先天性巨结肠(HD)和肠神经节细胞减少症(HYPG)肠壁中表达的免疫组化研究. 武汉:华中科技大学, 2007.
5.	Pan ZW, Li JC. Advances in molecular genetics of Hirschsprung's disease. Anat Rec (Hoboken), 2012, 295(10):1628-1638.
6.	孙树敏, 刘皓. 神经生长相关蛋白与突触可塑性. 天津医科大学学报, 2007, 13(1):118-121.
7.	Sharkey KA, Coggin PJ, Tetzlaff W, et al. Distribution of troth-associated protein, B-50 (GAP-43) in the mammalian enteric nervous system. Neuroscience, 1990, 38(1):13-20.
8.	Andreasen TJ, Luetje CW, Heideman W, et al. Purification of a novel calmodulin binding protein from bovine cerebral cortex membranes. Biochemistry, 1983, 22(20):4615-4618.
9.	刘健, 杨小玉, 杨茂光, 等. 中枢神经损伤后GAP-43蛋白对神经再生及轴突导向作用及其机制的研究进展. 吉林大学学报: 医学版, 2013, 39(1):180-183.
10.	栾永昕, 张剑涛, 付双林. 神经系统相关蛋白的研究进展. 中国老年学杂志, 2009, 29(16):2129-2132.
11.	帖利军, 潘建平, 宋天保, 等. GAP-43在发育大鼠中枢神经系统的表达. 西安医科大学学报, 2001, 22(6):499-501.
12.	崔新海, 陈雨历, 张蕾, 等. 先天性巨结肠突触素免疫组织化学研究. 中国现代普通外科进展, 2006, 9(6):340-342, 345.
13.	张康军. Semaphorin 5A在先天性巨结肠症中的表达. 遵义:遵义医学院, 2012.
14.	杜勇, 施诚仁, 潘骏, 等. 先天性巨结肠HuD蛋白表达的实验研究. 临床小儿外科杂志, 2005, 4(5):345-348.
15.	Pascale A, Gusev PA, Amadio M, et al. Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc Natl Acad Sci U S A, 2004, 101(5):1217-1222.
16.	Smith CL, Afroz R, Bassell GJ, et al. GAP-43 mRNA in growth cones is associated with HuD and ribosomes. J Neurobiol, 2004, 61(2):222-235.
17.	Kobayashi H, Hirakawa H, Puri P. Is intestinal neuronal dysplasia a disorder of the neuromuscular junction?. J Pediatr Surg, 1996, 31(4):575-579.
18.	Saeed A, Barreto L, Neogii SG, et al. Identification of novel genes in Hirschsprung disease pathway using whole genome expression study. J Pediatr Surg, 2012, 47(2):303-307.
19.	Grynspan D, Giassi AC, Cadonic R, et al. Growth-associated protein 43 (GAP-43) expression in ganglionic and aganglionic colon. Pediatr Dev Pathol, 2012, 15(5):428-429.

1. Mckeown SJ, Stamp L, Hao MM, et al. Hirschsprung disease:a developmental disorder of the enteric nervous system. Wiley Interdiscip Rev Dev Biol, 2013, 2(1):113-129.
2. 黎明, 肖雅玲. 120例先天性巨结肠发病危险因素分析及外科治疗. 中国医药导刊, 2013, 15(2): 259-261.
3. 刘鹏飞, 秦克旺, 吴坤河, 等. HAND2蛋白在先天性巨结肠肠壁肌间神经丛中的表达及意义. 广东医学, 2013, 34(10):1513-1515.
4. 覃宇冰. HuD蛋白在先天性巨结肠(HD)和肠神经节细胞减少症(HYPG)肠壁中表达的免疫组化研究. 武汉:华中科技大学, 2007.
5. Pan ZW, Li JC. Advances in molecular genetics of Hirschsprung's disease. Anat Rec (Hoboken), 2012, 295(10):1628-1638.
6. 孙树敏, 刘皓. 神经生长相关蛋白与突触可塑性. 天津医科大学学报, 2007, 13(1):118-121.
7. Sharkey KA, Coggin PJ, Tetzlaff W, et al. Distribution of troth-associated protein, B-50 (GAP-43) in the mammalian enteric nervous system. Neuroscience, 1990, 38(1):13-20.
8. Andreasen TJ, Luetje CW, Heideman W, et al. Purification of a novel calmodulin binding protein from bovine cerebral cortex membranes. Biochemistry, 1983, 22(20):4615-4618.
9. 刘健, 杨小玉, 杨茂光, 等. 中枢神经损伤后GAP-43蛋白对神经再生及轴突导向作用及其机制的研究进展. 吉林大学学报: 医学版, 2013, 39(1):180-183.
10. 栾永昕, 张剑涛, 付双林. 神经系统相关蛋白的研究进展. 中国老年学杂志, 2009, 29(16):2129-2132.
11. 帖利军, 潘建平, 宋天保, 等. GAP-43在发育大鼠中枢神经系统的表达. 西安医科大学学报, 2001, 22(6):499-501.
12. 崔新海, 陈雨历, 张蕾, 等. 先天性巨结肠突触素免疫组织化学研究. 中国现代普通外科进展, 2006, 9(6):340-342, 345.
13. 张康军. Semaphorin 5A在先天性巨结肠症中的表达. 遵义:遵义医学院, 2012.
14. 杜勇, 施诚仁, 潘骏, 等. 先天性巨结肠HuD蛋白表达的实验研究. 临床小儿外科杂志, 2005, 4(5):345-348.
15. Pascale A, Gusev PA, Amadio M, et al. Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc Natl Acad Sci U S A, 2004, 101(5):1217-1222.
16. Smith CL, Afroz R, Bassell GJ, et al. GAP-43 mRNA in growth cones is associated with HuD and ribosomes. J Neurobiol, 2004, 61(2):222-235.
17. Kobayashi H, Hirakawa H, Puri P. Is intestinal neuronal dysplasia a disorder of the neuromuscular junction?. J Pediatr Surg, 1996, 31(4):575-579.
18. Saeed A, Barreto L, Neogii SG, et al. Identification of novel genes in Hirschsprung disease pathway using whole genome expression study. J Pediatr Surg, 2012, 47(2):303-307.
19. Grynspan D, Giassi AC, Cadonic R, et al. Growth-associated protein 43 (GAP-43) expression in ganglionic and aganglionic colon. Pediatr Dev Pathol, 2012, 15(5):428-429.

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Expression of Growth Associated Protein-43 in Intestinal Tissues of Patients with Hirschsprung Disease

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