Articles
 

Effects of Mitochondrial ATP-Sensitive Potassium Channels on the Proliferation and Secretion of Human Airway Smooth Muscle Cells

Abstract

Bronchial asthma is the common chronic inflammatory disease and is characterized by chronic airway inflammation, airway remodeling, and airway hyperreactivity (AHR). Aim of this study was to investigate the effects of mitochondrial ATP-sensitive potassium channels (MitoKATP) on the proliferation and secretion of human airway smooth muscle cells (HASMCs). HASMCs were treated with the serum from asthmatic patients to establish HASMCs asthma model of passive sensitization. Rhodamine 123 (R-123) and 2,7-dichloro-dihydrofluorescein diacetate (DCFH-DA) fluorescence staining were used to detect mitochondrial membrane potential (Δψm) and the content of reactive oxygen species (ROS) in the cells, respectively. The cell counting was used to detect cell proliferation, and RT-PCR was used to detect the expression of TGF-β1 mRNA. In the normal + Diazoxide group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-β1 expression were enhanced, compared with the normal control group (p<0.05). There were no significant differences between the normal + 5-hydroxydecanoate (5-HD) group and the normal control group. In the asthma model control group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-β1 expression were enhanced, compared with normal control group, (p<0.05). The aforementioned indices were enhanced in the asthma model + Diazoxide group, when compared with the asthma model control group, whereas these indices were attenuated in the asthma model + 5-HD group, when compared with the asthma model control group (p<0.05). In conclusion, asthma could activate MitoKATP channels in HASMCs, promote HASMC proliferation and TGF-β1 expression.

1. McKay S, de Jongste JC, Saxena PR, Sharma HS.Angiotensin II induces hypertrophy of human airway smooth muscle cells: expression of transcription factors and transforming growth factor-beta1. Am J Respir Cell Mol Biol 1998; 18(6):823-33.
2. Panettieri RA. Airway smooth muscle: immunomodulatory cells that modulate airway remodeling? Respir Physiol Neurobiol 2003; 137(2-3):277-93.
3. Sukkar MB, Stanley AJ, Blake AE, Hodgkin PD, Johnson PR, Armour CL, et al. 'Proliferative' and 'synthetic' airway smooth muscle cells are overlapping populations. Immunol Cell Biol 2004; 82(5):471-8.
4. Akrouh A, Halcomb SE, Nichols CG, Sala-Rabanal M.Molecular biology of K(ATP) channels and implications for health and disease. IUBMB Life 2009; 61(10):971-8.
5. Zhao JP, Gao M, Ye YJ, Hu WH, Zhou ZG, Hu HL.Regulation of rat airway smooth muscle cell proliferation by mitochondrial ATP-sensitive K(+) channel in asthmic rats. Sheng Li Xue Bao 2009; 61(1):65-71.
6. National Asthma Education and Prevention Program.Expert Panel Report 3 (EPR-3). Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol 2007; 120(5):S94-138.
7. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008; 31(1):143-78.
8. Laporte JC, Moore PE, Baraldo S, Jouvin MH, Church TL, Schwartzman IN, et al. Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells. Am J Respir Crit Care Med. 2001; 164(1):141-8.
9. Johnson PR, Black JL, Carlin S, Ge Q, Underwood PA.The production of extracellular matrix proteins by human passively sensitized airway smooth-muscle cells in culture: the effect of beclomethasone. Am J Respir Crit Care Med 2000; 162(6):2145-51.
10. Krick S, Platoshyn O, McDaniel SS, Rubin LJ, Yuan JX.Augmented K(+) currents and mitochondrial membrane depolarization in pulmonary artery myocyte apoptosis. Am J Physiol Lung Cell Mol Physiol 2001; 281(4):L887-894.
11. Csonka C, Kupai K, Bencsik P, Görbe A, Pálóczi J, Zvara A, et al. Cholesterol-enriched Diet Inhibits Cardioprotection by Atp-sensitivepotassium Channel Activators Cromakalim and Diazoxide. Am J Physiol Heart Circ Physiol 2013. [Epub ahead of print]
12. Mironova GD, Negoda AE, Marinov BS, Paucek P, Costa AD, Grigoriev SM, et al. Functional distinctions between the mitochondrial ATP-dependent K+ channel (mitoKATP) and its inward rectifier subunit (mitoKIR). J Biol Chem 2004; 279(31):32562-8.
13. Constant-Urban C, Charif M, Goffin E, Van Heugen JC,Elmoualij B, Chiap P, et al. Triphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels. Bioorg Med Chem Lett 2013;23(21): 5878-81.
14. Ardehali H. Role of the mitochondrial ATP-sensitive K+channels in cardioprotection. Acta Biochim Pol 2004;51(2):379-90.
15. Das B, Sarkar C. Cardiomyocyte mitochondrial KATP channels participate in the antiarrhythmic and antiinfarct effects of KATP activators during ischemia and reperfusion in an intact anesthetized rabbit model. Pol J Pharmacol 2003; 55(5):771-86.
16. Minshall EM, Leung DY, Martin RJ, Song YL, Cameron L, Ernst P, et al. Eosinophil-associated TGF-eta1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 1997; 17(3):326-33.
17. Hara K, Hasegawa T, Ooi H, Koya T, Tanabe Y, Tsukada H, et al. Inhibitory role of eosinophils on cell surface plasmin generation by bronchial epithelial cells: inhibitory effects of transforming growth factor beta. Lung 2001; 179(1):9-20.
18. Yang ZC, Yi MJ, Ran N, Wang C, Fu P, Feng XY, et al.
Transforming growth factor-β1 induces bronchial epithelial cells to mesenchymal transition by activating the Snail pathway and promotes airway remodeling in asthma. Mol Med Rep 2013; 8(6):1663-8.
19. Firszt R, Francisco D, Church TD, Thomas JM, Ingram JL, Kraft M. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma. Eur Respir J 2013; 43(2):464-73.

Files
IssueVol 13, No 6 (2014) QRcode
SectionArticles
Keywords
Asthma smooth muscle Mitochondrial ATP-sensitive potassium channels(MitoKATP) Reactive oxygen species (ROS) Membrane potential

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Chen C, Wang R, Zhou S, Zhao J, Xu Y. Effects of Mitochondrial ATP-Sensitive Potassium Channels on the Proliferation and Secretion of Human Airway Smooth Muscle Cells. Iran J Allergy Asthma Immunol. 1;13(6):420-427?.