MAPK信号通路在慢性鼻-鼻窦炎伴鼻息肉和不伴鼻息肉的黏膜上皮修复机制中的作用

王彤; 臧洪瑞; 李云川; 李丽娟; 李立峰; 武骏; 胡长龙

doi:10.13201/j.issn.1001-1781.2018.21.004

MAPK信号通路在慢性鼻-鼻窦炎伴鼻息肉和不伴鼻息肉的黏膜上皮修复机制中的作用

- 首都医科大学附属北京同仁医院耳鼻咽喉头颈外科中心教育部省部共建重点实验室(北京, 100730)

详细信息

通讯作者: 臧洪瑞, E-mail:zanghongrui@126.com

中图分类号: R765.4

收稿日期: 2018-05-29

The role of MAPK signaling pathway in the repair of mucosal epithelium in chronic sinusitis with nasal polyps and without nasal polyps

- Key Laboratory Otolaryngology Head and Neck Surgery, Capital Medical University, Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital Affiliated to the Capital University of Medical Science, Beijing, 100730, China

More Information

Corresponding author: ZANG Hongrui, E-mail: zanghongrui@126.com

Received Date: 29 May 2018

摘要

摘要: 目的: 探讨细胞分裂素活化蛋白激酶(MAPK)信号通路在慢性鼻-鼻窦炎不伴鼻息肉(CRSsNP)和慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)的黏膜上皮细胞修复中的作用。方法: 通过MTT法检测正常对照组、CRSsNP组和CRSwNP组体外原代细胞培养的鼻窦上皮细胞分别在加入表皮生长因子(EGF)及其受体(EGFR)激酶抑制剂AG1478和胞外信号调节激酶ERK1/2抑制剂PD98059后的增殖水平;用Western blot法定量检测ERK1/2及其磷酸化水平的差异。结果: CRS黏膜上皮细胞的增殖基线水平和对EGF的增殖反应低于正常对照组。CRSsNP组:AG1478对EGF增殖作用的抑制明显大于PD98059。CRSwNP组:AG1478能够抑制EGF对上皮细胞的增殖作用,而PD98059没有明显抑制作用。CRS黏膜上皮细胞ERK1/2磷酸化率低于对照组,并且在CRSwNP中表达更低。结论: MAPK通路对鼻黏膜上皮细胞增殖作用在CRS中减弱,尤其是CRSwNP更弱,可能是CRS黏膜上皮细胞的修复能力受到抑制的原因之一。在CRSwNP中当MAPK通路被阻断时,可能有其他途径补偿了对上皮细胞的修复作用。
- 鼻窦炎 /
- 上皮修复 /
- 表皮生长因子受体 /
- 细胞分裂素活化蛋白激酶信号通路
Abstract: Objective: To evaluate the differences between CRS and normal subjects and between chronic rhinosinusitis without nasal polys(CRSsNP) and chronic rhinosinusitis with nasal polys(CRSwNP) in the regulation of EGF pathways and the regulating proliferative position of MAPK pathways.Method: We evaluated the proliferation rates of ethmoidal mucosal cells before and after stimulation with EGF, epidermal growth factor receptor(EGFR) kinase inhibitor AG1478, and extracellular signal-regulated kinase 1/2(ERK1/2) inhibitorPD98059 using MTT assays. We also analyzed the sinonasal epithelial cells collected from control subjects and patients with CRS subtypes CRSsNP and CRSwNP for the expression of ERK1/2, phosphorylated ERK1/2 using western blot analyses.Result: The proliferation rates of sinonasal epithelial cells before and after EGF stimulation were lower in CRS patients than in the controls. AG1478 or PD98059 inhibitor treatment of control epithelial cells did not result in a significant difference in proliferation. Although, AG1478 and PD98059 inhibited the proliferation of CRS cells, the level of proliferation inhibition was markedly different in CRSsNP. AG1478 suppressed the proliferation of CRSwNP epithelial cells, whereas PD98059 had no effect. The ratio of ERK1/2 phosphorylation in CRS cells was lower than that of the control cells.Conclusion: MAPK classical pathway and other pathways might be active at the same time to stimulate epithelial cell proliferation in CRSsNP. When the classical pathway was blocked in CRSwNP, some other pathway could have completely compensated the proliferation.
- sinusitis /
- epithelial repair /
- epidermal growth factor /
- MAPK pathway

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参考文献(13)

[1]	STEVENS W W, LEE R J, SCHLEIMER R P, et al.Chronic rhinosinusitis pathogenesis[J].J Allergy ClinImmunol, 2015, 136:1442-1453.
[2]	GON Y, HASHIMOTO S.Role of airway epithelial barrier dysfunction in pathogenesis of asthma[J].Allergol Int, 2018, 67:12-17.
[3]	WATELET J B, DOGNE J M, MULLIER F.Remodeling and repair in rhinosinusitis[J].Curr Allergy Asthma Rep, 2015, 15:34-39.
[4]	CERESA B P, PETERSON J L.Cell and molecular biology of epidermal growth factor receptor[J].Int Rev Cell Mol Biol, 2014, 313:145-78.
[5]	DING G Q, ZHENG C Q, BAGGA S S.Up-regulation of the mucosal epidermal growth factor receptor gene in chronic rhinosinusitis and nasal polyposis[J].Arch Otolaryngol Head Neck Surg, 2007, 133:1097-1099.
[6]	LI Y, LI L, WANG T, et al.Analysis of epidermal growth factor signaling in nasal mucosa epithelial cell proliferation involved in chronic rhinosinusitis[J].Chin Med J (Engl), 2014, 127:3449-3453.
[7]	FOKKENS W J, LUND V J, MULLOL J, et al.EPOS 2012:European position paper on rhinosinusitis and nasal polyps 2012.A summary for otorhinolaryngologists[J].Rhinology, 2012, 50:1-5.
[8]	王彤, 李云川, 臧洪瑞, 等.不伴鼻息肉的慢性鼻及鼻窦炎黏膜重构的组织病理学研究[J].中国耳鼻咽喉头颈外科杂志, 2010, 17 (5):261-164.
[9]	JONES S, RAPPOPORT J Z.Interdependent epidermal growth factor receptor signalling and trafficking[J].Int J Biochem Cell Biol, 2014, 51:23-28.
[10]	王振霖, 李源, 杨秀海, 等.慢性鼻-鼻窦炎中鼻甲黏膜环氧合酶2与上游丝裂原激活蛋白激酶及核因子κB信号通路相关性探讨[J].中华耳鼻咽喉头颈外科杂志, 2007, 46 (6):447-451.
[11]	范隽, 赵昌敏, 刘兆芳, 等.p38MAPK信号通路调控IL-6、HIF-1α及VEGF对慢性鼻-鼻窦炎发病机制的影响[J].中国当代医药, 2017, 9 (1):8-11.
[12]	YAGUBLU V, AHMADOVA Z, HAJIYEVA Y, et al.Combination of the EGFR tyrosine kinase inhibitor AG1478 and 5-FU:no synergistic effect on EGFRphosphorylation, cell proliferation and apoptosis induction[J].Anticancer Res, 2013, 33:3753-3758.
[13]	KAWABATA T, TOKUDA H, FUJITA K, et al.Resveratrol inhibits the epidermal growth factor-induced migration of osteoblasts:the suppression of SAPK/JNK and Akt[J].Cell Physiol Biochem, 2017, 43:1025-1036.