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CLC number: R574.4

On-line Access: 2016-01-06

Received: 2015-06-27

Revision Accepted: 2015-11-07

Crosschecked: 2015-12-16

Cited: 11

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xiao-juan Xu

http://orcid.org/0000-0002-3797-0567

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Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.1 P.1-9

http://doi.org/10.1631/jzus.B1500181


Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?


Author(s):  Xiao-juan Xu, Liang Liu, Shu-kun Yao

Affiliation(s):  1Gastroenterology Department, China-Japan Friendship Hospital, Beijing 100029, China; more

Corresponding email(s):   Ysk12329@126.com

Key Words:  Nerve growth factor, Diarrhea-predominant irritable bowel syndrome, Pathophysiology, Intestinal barrier dysfunction, Visceral hypersensitivity


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Xiao-juan Xu, Liang Liu, Shu-kun Yao. Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?[J]. Journal of Zhejiang University Science B, 2016, 17(1): 1-9.

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author="Xiao-juan Xu, Liang Liu, Shu-kun Yao",
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volume="17",
number="1",
pages="1-9",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1500181"
}

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%T Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?
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%A Liang Liu
%A Shu-kun Yao
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T1 - Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1500181


Abstract: 
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

神经生长因子与腹泻型肠易激综合征:具有前景的治疗靶点?

目的:回顾国内外研究进展,针对神经生长因子(NGF)在腹泻型肠易激综合征(IBS-D)病理生理学,尤其在内脏高敏感和肠屏障功能受损中的作用作一综述。
创新点:总结了国内外有关NGF参与IBS-D病理生理学的基础及临床研究证据,提出了NGF介导IBS-D内脏高敏感和肠屏障功能受损的可能机制,并首次构建了NGF-肥大细胞-神经纤维三者在IBS-D发病中的作用网络。
方法:在PubMed、EMBASE、Web of Science、CNKI、维普和万方等数据库检索有关NGF参与IBS-D病理生理学的中英文文献,时间设定为各数据库建库至2015年5月。剔除重复及不相关文献后,对纳入文献进行综述。
结论:NGF作为重要的神经内分泌介质,可能参与介 导了IBS-D患者内脏高敏感和肠屏障功能受损,其在IBS-D病理生理学中的作用值得深入研究,并有望成为治疗靶点。

关键词:神经生长因子;腹泻型肠易激综合征;病理生理学;内脏高敏感;肠屏障功能受损

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Akbar, A., Yiangou, Y., Facer, P., et al., 2008. Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut, 57(7):923-929.

[2]Barbara, G., Stanghellini, V., de Giorgio, R., et al., 2004. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, 126(3):693-702.

[3]Barbara, G., Wang, B., Stanghellini, V., et al., 2007. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology, 132(1):26-37.

[4]Barreau, F., Cartier, C., Ferrier, L., et al., 2004. Nerve growth factor mediates alterations of colonic sensitivity and mucosal barrier induced by neonatal stress in rats. Gastroenterology, 127(2):524-534.

[5]Barreau, F., Cartier, C., Leveque, M., et al., 2007. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay. J. Physiol., 580(1):347-356.

[6]Barreau, F., Salvador-Cartier, C., Houdeau, E., et al., 2008. Long-term alterations of colonic nerve-mast cell interactions induced by neonatal maternal deprivation in rats. Gut, 57(5):582-590.

[7]Bischoff, S.C., Barbara, G., Buurman, W., et al., 2014. Intestinal permeability—a new target for disease prevention and therapy. BMC Gastroenterol., 14(1):189.

[8]Bonnington, J.K., McNaughton, P.A., 2003. Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J. Physiol., 551(2):433-446.

[9]Bothwell, M., 2014. NGF, BDNF, NT3, and NT4. In: Lewin, G.R., Carter, B.D. (Eds.), Neurotrophic Factors. Springer Berlin Heidelberg, p.3-15.

[10]Bramson, C., Herrmann, D.N., Carey, W., et al., 2015. Exploring the role of tanezumab as a novel treatment for the relief of neuropathic pain. Pain Med., 16(6):1163-1176.

[11]Camilleri, M., 2012. Peripheral mechanisms in irritable bowel syndrome. N. Engl. J. Med., 367(17):1626-1635.

[12]Cenac, N., Andrews, C.N., Holzhausen, M., et al., 2007. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin. Invest., 117(3):636-647.

[13]Chang, L., Sundaresh, S., Elliott, J., et al., 2009. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterol. Motil., 21(2):149-159.

[14]Choung, R.K., Locke, G.R., 2011. Epidemiology of IBS. Gastroenterol. Clin. N. Am., 40(1):1-10.

[15]Coëffier, M., Gloro, R., Boukhettala, N., et al., 2010. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am. J. Gastroenterol., 105(5):1181-1188.

[16]Coelho, A., Wolf-Johnston, A.S., Shinde, S., et al., 2015. Urinary bladder inflammation induces changes in urothelial nerve growth factor and vanilloid receptor 1. Br. J. Pharmacol., 172(7):1691-1699.

[17]Delafoy, L., Raymond, F., Doherty, A.M., et al., 2003. Role of nerve growth factor in the trinitrobenzene sulfonic acid-induced colonic hypersensitivity. Pain, 105(3):489-497.

[18]Delafoy, L., Gelot, A., Ardid, D., et al., 2006. Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat. Gut, 55(7):940-945.

[19]di Mola, F.F., Friess, H., Zhu, Z.W., et al., 2000. Nerve growth factor and Trk high affinity receptor (TrkA) gene expression in inflammatory bowel disease. Gut, 46(5):670-678.

[20]Dothel, G., Barbaro, M.R., Boudin, H., et al., 2015. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology, 148(5):1002-1011.

[21]Evans, R.J., Moldwin, R.M., Cossons, N., et al., 2011. Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis. J. Urol., 185(5):1716-1721.

[22]Ferrier, L., Mazelin, L., Cenac, N., et al., 2003. Stress-induced disruption of colonic epithelial barrier: role of interferon-γ and myosin light chain kinase in mice. Gastroenterology, 125(3):795-804.

[23]Gimbel, J.S., Kivitz, A.J., Bramson, C., et al., 2014. Long-term safety and effectiveness of tanezumab as treatment for chronic low back pain. Pain, 155(9):1793-1801.

[24]Hao, J.X., Duan, L.P., 2010. Progress in the relationship of intestinal mucosal barrier function and irritable bowel syndrome. Chin. J. Dig., 30(11):861-863 (in Chinese).

[25]Keita, A.V., Söderholm, J.D., 2010. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol. Motil., 22(7):718-733.

[26]Kennedy, P.J., Cryan, J.F., Quigley, E.M., et al., 2014. A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome. Psychol. Med., 44(14):3123-3134.

[27]Lee, H., Park, J.H., Park, D.I., et al., 2013. Mucosal mast cell count is associated with intestinal permeability in patients with diarrhea predominant irritable bowel syndrome. J. Neurogastroenterol. Motil., 19(2):244-250.

[28]Leon, A., Buriani, A., Dal Toso, R., et al., 1994. Mast cells synthesize, store, and release nerve growth factor. PNAS, 91(9):3739-3743.

[29]Levi-Montalcini, R., Skaper, S.D., Dal Toso, R., et al., 1996. Nerve growth factor: from neurotrophin to neurokine. Trends Neurosci., 19(11):514-520.

[30]Lewin, G.R., Lechner, S.G., Smith, E.S., 2014. Nerve growth factor and nociception: from experimental embryology to new analgesic therapy. In: Lewin, G.R., Carter, B.D. (Eds.), Neurotrophic Factors. Springer Berlin Heidelberg, p.251-282.

[31]Li, Q., Xu, C.P., Yang, M., et al., 2014. Expression and significance of nerve growth factor in ulcerative colitis. Chin. J. Gastroenterol., 19(10):593-595 (in Chinese).

[32]Liu, L., Liu, B.N., Chen, S., et al., 2014. Visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction and low-grade inflammation in a subset of irritable bowel syndrome patients. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 15(10):907-914.

[33]Martínez, C., Lobo, B., Pigrau, M., et al., 2013. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut, 62(8):1160-1168.

[34]Mayer, E.A., 2000. The neurobiology of stress and gastrointestinal disease. Gut, 47(6):861-869.

[35]Mujagic, Z., Ludidi, S., Keszthelyi, D., et al., 2014. Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders. Aliment. Pharmacol. Ther., 40(3):288-397.

[36]Neunlist, M., Toumi, F., Oreschkova, T., et al., 2003. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am. J. Physiol. Gastrointest. Liver Physiol., 285(5):G1028-G1036.

[37]Nickel, J.C., Atkinson, G., Krieger, J.N., et al., 2012. Preliminary assessment of safety and efficacy in proof-of-concept, randomized clinical trial of tanezumab for chronic prostatitis/chronic pelvic pain syndrome. Urology, 80(5):1105-1110.

[38]Ohashi, K., Sato, Y., Kawai, M., et al., 2008. Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats. Life Sci., 82(7-8):419-423.

[39]Overman, E.L., Rivier, J.E., Moeser, A.J., 2012. CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α. PLoS ONE, 7(6):e39935.

[40]Park, C.H., Joo, Y.E., Choi, S.K., 2003. Activated mast cell infiltrate in close proximity to enteric nerves in diarrhea-predominant irritable bowel syndrome. J. Korean Med. Sci., 18(2):204-210.

[41]Piche, T., Barbara, G., Aubert, P., et al., 2009. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut, 58(2):196-201.

[42]Rukwied, R., Mayer, A., Kluschina, O., et al., 2010. NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity inhuman skin. Pain, 148(3):407-413.

[43]Sanga, P., Katz, N., Polverejan, E., et al., 2013. Efficacy, safety, and tolerability of fulranumab, an anti-nerve growth factor antibody, in the treatment of patients with moderate to severe osteoarthritis pain. Pain, 154(10):1910-1919.

[44]Shen, F., Li, D.G., Zhou, H.Q., 2011. An epidemiological investigation of irritable bowel syndrome in Shanghai Songjiang communities. Chin. J. Dig., 31(10):663-668 (in Chinese).

[45]Shulman, R.J., Jarrett, M.E., Cain, K.C., et al., 2014. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. J. Gastroenterol., 49(11):1467-1476.

[46]Skaper, S.D., Pollock, M., Facci, L., 2001. Mast cells differentially express and release active high molecular weight neurotrophins. Mol. Brain Res., 97(2):177-185.

[47]Snider, W.D., McMahon, S.B., 1998. Tackling pain at the source: new ideas about nociceptors. Neuron, 20(4):629-632.

[48]Stein, A.T., Ufret-Vincenty, C.A., Hua, L., et al., 2006. Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J. Gen. Physiol., 128(5):509-522.

[49]Tiseo, P.J., Kivitz, A.J., Ervin, J.E., et al., 2014. Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of pain: results from a double-blind, placebo-controlled exploratory study in osteoarthritis of the knee. Pain, 155(7):1245-1252.

[50]van den Wijngaard, R.M., Klooker, T.K., Welting, O., et al., 2009. Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. Neurogastroenterol. Motil., 21(10):1107-e94.

[51]Wang, W.L., Wu, W.C., 2010. Nerve growth factor and irritable bowel syndrome. Chin. J. Gastroenterol. Hepatol., 19(3):285-287 (in Chinese).

[52]Willot, S., Gauthier, C., Patey, N., et al., 2012. Nerve growth factor content is increased in the rectal mucosa of children with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol. Motil., 24(8):734-e347.

[53]Yao, X., Yang, Y.S., Zhao, K.B., et al., 2008. Clinical features and subtypes of irritable bowel syndrome based on Rome III diagnostic criteria. World Chin. J. Digestol., 16(5):563-566 (in Chinese).

[54]Yu, Y., Gao, J., Zhang, W., et al., 2008. Effect of nerve growth factor on colorectal visceral hypersensitivity in rats. Chin. J. Dig., 28(11):764-766 (in Chinese).

[55]Zhang, L., Duan, L.P., Liu, Y.X., et al., 2014. A meta-analysis of the prevalence and risk factors of irritable bowel syndrome in Chinese community. Chin. J. Intern. Med., 53(12):969-975 (in Chinese).

[56]Zhou, Q.Q., Zhang, B.Y., Verne, G.N., 2009. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain, 146(1-2):41-46.

[57]Zhou, X.P., Li, X.L., 2014. Advances in studies on visceral hypersensitivity of irritable bowel syndrome. Chin. J. Gastroenterol., 19(2):117-119 (in Chinese).

[58]Zhu, W., Oxford, G.S., 2007. Phosphoinositide-3-kinase and mitogen activated protein kinase signaling pathways mediate acute NGF sensitization of TRPV1. Mol. Cell. Neurosci., 34(4):689-700.

[59]Zhuang, Z.Y., Xu, H., Clapham, D.E., et al., 2004. Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J. Neurosci., 24(38):8300-8309.

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