Role of the extracellular signal-regulated kinase 1/2 signaling pathway in the process of thrombin-promoting airway remodeling in ovalbumin-allergic rats

被引：8

作者：

Bi, Meirong ^{[1
]}

Guo, Aili ^{[1
]}

Zhao, Hongyang ^{[1
]}

Sun, Xuewu ^{[2
]}

Chen, Qiang ^{[3
]}

Yu, Li ^{[4
]}

Shi, Wei ^{[5
]}

Wang, Yan ^{[6
]}

Shen, Guohong ^{[1
]}

Wang, Xueying ^{[1
]}

Zhao, Yingchun ^{[1
]}

Zhang, Nan ^{[1
]}

Xu, Mi ^{[1
]}

Qin, Mingming ^{[1
]}

Zhu, Weiwei ^{[1
]}

机构：

[1] Shandong Univ, Jinan Cent Hosp, Dept Pediat, Jinan, Shandong, Peoples R China

[2] Shandong Univ, Jinan Cent Hosp, Dept Burn & Plast, Jinan, Shandong, Peoples R China

[3] Shandong Univ, Jinan Cent Hosp, Dept Tradit Chinese Med, Jinan, Shandong, Peoples R China

[4] Shandong Univ, Jinan Cent Hosp, Dept Otorhinolaryngol, Jinan, Shandong, Peoples R China

[5] Shandong Univ, Jinan Cent Hosp, Dept Obstet & Gynaecol, Jinan, Shandong, Peoples R China

[6] Shandong Univ, Jinan Cent Hosp, Med Lab Diagnost Ctr, Jinan, Shandong, Peoples R China

来源：

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY | 2015年 / 37卷 / 01期

关键词：

Airway remodeling; asthma; PD98059; pERK1/2; rat; thrombin; PROTEASE-ACTIVATED RECEPTORS; MUSCLE-CELL-PROLIFERATION; CHRONIC ASTHMATIC RATS; SMOOTH-MUSCLE; INFLAMMATION; EXPRESSION; MICE; MIGRATION; FIBROSIS; ANTIGEN;

D O I：

10.3109/08923973.2014.993083

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Context: Although it is recognized that thrombin plays a key role in airway remodeling during chronic asthma. In a previous study, we have proved that thrombin promotes airway remodeling via PAR-1 in OVA-allergic rats, but little is known about intracellular signaling pathway involved in the event. Objective: In this study, we intend to explore the impact of pERK1/2 signaling pathway on the process of thrombin-induced airway remodeling in OVA-allergic rats. Materials and methods: A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06, and pERK1/2 inhibitor PD98059 varied for different groups. The expression of pERK1/2 was analyzed by western blot and RT-PCR. Secretion of TGF-beta 1 and IL-6 was detected by ELISA. Results: The expression of pERK1/2 was higher in the airway of asthmatic rats than those of normal rats, and was significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was enhanced by thrombin but weakened by pERK1/2 inhibitor. Expression of growth factors and IL-6 in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and pERK1/2 inhibitor treatment. Conclusion: These results suggest that ERK1/2 signaling pathway may play an important role in the process of thrombin-promoting airway remodeling in OVA-allergic rats, and pERK1/2 inhibitor effectively inhibits the process.

引用

页码：26 / 34

页数：9

共 37 条

[1] Effect of IL-6 trans-signaling on the pro-remodeling phenotype of airway smooth muscle [J].

Ammit, Alaina J. ;

Moir, Lyn M. ;

Oliver, Brian G. ;

Hughes, J. Margaret ;

Alkhouri, Hatem ;

Ge, Qi ;

Burgess, Janette K. ;

Black, Judith L. ;

Roth, Michael .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2007, 292 (01) :L199-L206

[2]

Bai Jing, 2007, Shengli Xuebao, V59, P311

[3] Asthma - From bronchoconstriction to airways inflammation and remodeling [J].

Bousquet, J ;

Jeffery, PK ;

Busse, WW ;

Johnson, M ;

Vignola, AM .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (05) :1720-1745

[4] Thrombin promotes proinflammatory phenotype in human vascular smooth muscle cell [J].

Chung, Sung-Woon ;

Park, Jae-Woo ;

Lee, Sae-A ;

Eo, Seong-Kug ;

Kim, Koanhoi .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 396 (03) :748-754

[5] Targeting Protease-Activated Receptor-1 with Cell-Penetrating Pepducins in Lung Cancer [J].

Cisowski, Jaroslaw ;

O'Callaghan, Katie ;

Kuliopulos, Athan ;

Yang, John ;

Nga Nguyen ;

Deng, Qing ;

Yang, Eric ;

Fogel, Michael ;

Tressel, Sarah ;

Foley, Caitlin ;

Agarwal, Anika ;

Hunt, Stephen W., III ;

McMurry, Tom ;

Brinckerhoff, Larry ;

Covic, Lidija .

AMERICAN JOURNAL OF PATHOLOGY, 2011, 179 (01) :513-523

[6] AIRWAY EPITHELIAL-CELL EXPRESSION OF INTERLEUKIN-6 IN TRANSGENIC MICE - UNCOUPLING OF AIRWAY INFLAMMATION AND BRONCHIAL HYPERREACTIVITY [J].

DICOSMO, BF ;

GEBA, GP ;

PICARELLA, D ;

ELIAS, JA ;

RANKIN, JA ;

STRIPP, BR ;

WHITSETT, JA ;

FLAVELL, RA .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (05) :2028-2035

[7] Progress in the understanding of protease-activated receptors [J].

Gabazza, EC ;

Taguchi, O ;

Kamada, H ;

Hayashi, T ;

Adachi, Y ;

Suzuki, K .

INTERNATIONAL JOURNAL OF HEMATOLOGY, 2004, 79 (02) :117-122

[8] Interferons modulate mitogen-induced protein synthesis in airway smooth muscle [J].

Goncharova, Elena A. ;

Lim, Poay N. ;

Chisolm, Amelia ;

Fogle, Homer W., III ;

Taylor, Jerome H. ;

Goncharov, Dmitry A. ;

Eszterhas, Andrew ;

Panettieri, Reynold A., Jr. ;

Krymskaya, Vera P. .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2010, 299 (01) :L25-L35

[9] α-thrombin stimulates contraction of human bronchial rings by activation of protease-activated receptors [J].

Hauck, RW ;

Schulz, C ;

Schömig, A ;

Hoffman, RK ;

Panettieri, RA .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1999, 277 (01) :L22-L29

[10] Platelet membranes induce airway smooth muscle cell proliferation [J].

Holm, Ann-Charlotte B. Svensson ;

Bengtsson, Torbjorn ;

Grenegard, Magnus ;

Lindstrom, Eva G. .

PLATELETS, 2011, 22 (01) :45-55

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