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例先天性巨結腸發病危險因素分析及外科治療. 中國醫藥導刊, 2013, 15(2): 259-261.
3.	劉鵬飛, 秦克旺, 吳坤河, 等. HAND2蛋白在先天性巨結腸腸壁肌間神經叢中的表達及意義. 廣東醫學, 2013, 34(10):1513-1515.
4.	覃宇冰. HuD蛋白在先天性巨結腸(HD)和腸神經節細胞減少癥(HYPG)腸壁中表達的免疫組化研究. 武漢:華中科技大學, 2007.
5.	Pan ZW, Li JC. Advances in molecular genetics of Hirschsprung's disease. Anat Rec (Hoboken), 2012, 295(10):1628-1638.
6.	孫樹敏, 劉皓. 神經生長相關蛋白與突觸可塑性. 天津醫科大學學報, 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.	劉健, 楊小玉, 楊茂光, 等. 中樞神經損傷后GAP-43蛋白對神經再生及軸突導向作用及其機制的研究進展. 吉林大學學報: 醫學版, 2013, 39(1):180-183.
10.	欒永昕, 張劍濤, 付雙林. 神經系統相關蛋白的研究進展. 中國老年學雜志, 2009, 29(16):2129-2132.
11.	帖利軍, 潘建平, 宋天保, 等. GAP-43在發育大鼠中樞神經系統的表達. 西安醫科大學學報, 2001, 22(6):499-501.
12.	崔新海, 陳雨歷, 張蕾, 等. 先天性巨結腸突觸素免疫組織化學研究. 中國現代普通外科進展, 2006, 9(6):340-342, 345.
13.	張康軍. Semaphorin 5A在先天性巨結腸癥中的表達. 遵義:遵義醫學院, 2012.
14.	杜勇, 施誠仁, 潘駿, 等. 先天性巨結腸HuD蛋白表達的實驗研究. 臨床小兒外科雜志, 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例先天性巨結腸發病危險因素分析及外科治療. 中國醫藥導刊, 2013, 15(2): 259-261.
3. 劉鵬飛, 秦克旺, 吳坤河, 等. HAND2蛋白在先天性巨結腸腸壁肌間神經叢中的表達及意義. 廣東醫學, 2013, 34(10):1513-1515.
4. 覃宇冰. HuD蛋白在先天性巨結腸(HD)和腸神經節細胞減少癥(HYPG)腸壁中表達的免疫組化研究. 武漢:華中科技大學, 2007.
5. Pan ZW, Li JC. Advances in molecular genetics of Hirschsprung's disease. Anat Rec (Hoboken), 2012, 295(10):1628-1638.
6. 孫樹敏, 劉皓. 神經生長相關蛋白與突觸可塑性. 天津醫科大學學報, 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. 劉健, 楊小玉, 楊茂光, 等. 中樞神經損傷后GAP-43蛋白對神經再生及軸突導向作用及其機制的研究進展. 吉林大學學報: 醫學版, 2013, 39(1):180-183.
10. 欒永昕, 張劍濤, 付雙林. 神經系統相關蛋白的研究進展. 中國老年學雜志, 2009, 29(16):2129-2132.
11. 帖利軍, 潘建平, 宋天保, 等. GAP-43在發育大鼠中樞神經系統的表達. 西安醫科大學學報, 2001, 22(6):499-501.
12. 崔新海, 陳雨歷, 張蕾, 等. 先天性巨結腸突觸素免疫組織化學研究. 中國現代普通外科進展, 2006, 9(6):340-342, 345.
13. 張康軍. Semaphorin 5A在先天性巨結腸癥中的表達. 遵義:遵義醫學院, 2012.
14. 杜勇, 施誠仁, 潘駿, 等. 先天性巨結腸HuD蛋白表達的實驗研究. 臨床小兒外科雜志, 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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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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

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