Effects of Mechanical Stretch on Expression of Airway Remodeling Associated Factors in Human Bronchial Epithelioid Cells_Journal of Biomedical Engineering

Authors：

YUQian ,  LIMinchao

Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China;

Corresponding author：

LIMinchao, Email: liminc66@aliyun.com

Keywords：

mechanical stretch; human bronchial epithelial cells; transforming growth factor-β1; fibroblast growth factor-2

DOI：

10.7507/1001-5515.20160149

Video：

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Abstract Full text Figures/Tables Video References Cited by

This study is aimed to investigate the effects of mechanical stretch on the expression of transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-2 (FGF-2), and the signaling pathway in human bronchial epithelioid (16HBE) cells under mechanical stretch. Using loading device with flexible substrate (FX-4000T) to stretch 16HBE cells, we found that the stretching elongation was 15%, at frequency of 1 Hz, stretching for 0.5 h, 1 h, 1.5 h and 2 h. Choosing the higher expression of TGF-β1, FGF-2 and Ca²⁺ group to carry out intervention experiments, we used the cells pretreated with canonical transient receptor potential 1 (TRPC1) channel antagonist SKF96365, protein kinase C (PKC) inhibitor HA-100, and thereafter mechanical stretch to interpose. Compared with those in the blank control group, TGF-β1 and FGF-2' protein and mRNA, intracellular Ca²⁺ fluorescence intensity were higher, and the differences were statistically significant (P < 0.05) at the 4 time points, 0.5 h, 1 h, 1.5 h and 2 h. At 0.5 h, the increasing rate was the highest. TGF-β1 protein and mRNA, FGF-2 protein and mRNA, intracellular Ca²⁺ luorescence intensity in the stretch+SKF96365 and stretch+HA-100 intervented group were decreased, the differences were statistically significant than those in 0.5 h stretch group (P < 0.05) without intervention. The expression of TGF-β1, FGF-2 was up-regulated in 16HBE cells under mechanical stretch, PKC, TRPC1, and Ca²⁺ may participate in the signal path.

Citation： YU Qian, LI Minchao. Effects of Mechanical Stretch on Expression of Airway Remodeling Associated Factors in Human Bronchial Epithelioid Cells. Journal of Biomedical Engineering, 2016, 33(5): 923-930. doi: 10.7507/1001-5515.20160149 Copy

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8.	GLAZEBROOK P A, SCHILLING W P, KUNZE D L. TRPC channels as signal transducers[J]. Pflugers Arch, 2005, 451(1):125-130.
9.	ALBERT A P. Gating mechanisms of canonical transient receptor potential Channel proteins:role of phosphoinositols and diacylglycerol[J]. Adv Exp Med Biol, 2011, 704:391-411.
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11.	FAYON M, REBOLA M, BERGER P, et al. Increased secretion of leukemia inhibitory factor by immature airway smooth[J]. Am J Physiol Lung Cell Mol Physiol, 2006, 291(2):244-294.
12.	PARK J E, LYON A R, SHAO D, et al. Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models[J]. Thorax, 2014, 69(12):1120-1126.
13.	MURATA N, ITO S, FURUYA K, et al. Ca²⁺ influx and ATP release mediated by mechanical stretch in human lung fibroblasts[J]. Biochem Biophys Res Commun, 2014, 453(1):101-105.
14.	OOMEN P, LOERAKKER S, VAN GEEMEN D, et al. Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling[J]. Acta Biomater, 2016, 29:161-169.
15.	LINDNER D, ZIETSCH C, TANK J, et al. Cardiac fibroblasts support cardiac inflammation in heart failure[J]. Basic Res Cardiol, 2014, 109(5):428.
16.	KRIZAJ D, RYSKAMP D A, TIAN Ning, et al. From mechanosensitivity to inflammatory responses:new players in the pathology of glaucoma[J]. Curr Eye Res, 2014, 39(2):105-119.
17.	AL M S, JOHNSON J R, HAMID Q. Remodeling in asthma[J]. Journal of Allergy and Clinical Immunology, 2011, 128:451-462.
18.	DURRANI S R, VISWANATHAN R K, BUSSE W W. What effect does asthma treatment have on airway remodeling? Current perspectives[J]. J Allergy Clin Immunol, 2011, 128(3):439-448; quiz 449-50.
19.	NILIUS B, DROOGMANS G, WONDERGEM R. Transient receptor potential channels in endothelium:solving the Calcium entry puzzle?[J]. Endothelium, 2003, 10(1):5-15.

1. SUKI B, SATO S, PARAMESWARAN H, et al. Emphysema and mechanical Stress-Induced lung remodeling[J]. Physiology, 2013, 28(6):404-413.
2. REEVES S R, KOLSTAD T, LIEN T Y, et al. Asthmatic airway epithelial cells differentially regulate fibroblast expression of extracellular matrix components[J]. Journal of Allergy and Clinical Immunology, 2014, 134(3):663-670.
3. BISSONNETTE É, MADORE A M, CHAKIR J, et al. Fibroblast growth factor-2 is a sputum remodeling biomarker of severe asthma[J]. Journal of Asthma, 2014, 51(2):119-144.
4. AL-ALAWI M, HASSAN T, CHOTIRMALL S H. Transforming growth factor beta and severe asthma:A perfect storm[J]. Respir Med, 2014, 108(10):1409-1423.
5. YANG Yucheng, ZHANG Nan, VAN CROMBRUGGEN K, et al. Transforming growth factor-beta1 in inflammatory airway disease:a key for understanding inflammation and remodeling[J]. Allergy, 2012, 67(10):1193-1202.
6. DOSANJH A. The fibroblast growth factor pathway and its role in the pathogenesis of lung disease[J]. J Interferon Cytokine Res, 2012, 32(3):111-114.
7. STAAF S, MAXVALL I, LIND U, et al. Down regulation of TRPC1 by shRNA reduces mechanosensitivity in mouse dorsal root ganglion neurons in vitro[J]. Neurosci Lett, 2009, 457(1):3-7.
8. GLAZEBROOK P A, SCHILLING W P, KUNZE D L. TRPC channels as signal transducers[J]. Pflugers Arch, 2005, 451(1):125-130.
9. ALBERT A P. Gating mechanisms of canonical transient receptor potential Channel proteins:role of phosphoinositols and diacylglycerol[J]. Adv Exp Med Biol, 2011, 704:391-411.
10. ITO S, KUME H, NARUSE K, et al. A novel Ca(2+) influx pathway activated by mechanical stretch in human airway smooth muscle cells[J]. Am J Respir Cell Mol Biol, 2008, 38(4):407-413.
11. FAYON M, REBOLA M, BERGER P, et al. Increased secretion of leukemia inhibitory factor by immature airway smooth[J]. Am J Physiol Lung Cell Mol Physiol, 2006, 291(2):244-294.
12. PARK J E, LYON A R, SHAO D, et al. Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models[J]. Thorax, 2014, 69(12):1120-1126.
13. MURATA N, ITO S, FURUYA K, et al. Ca²⁺ influx and ATP release mediated by mechanical stretch in human lung fibroblasts[J]. Biochem Biophys Res Commun, 2014, 453(1):101-105.
14. OOMEN P, LOERAKKER S, VAN GEEMEN D, et al. Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling[J]. Acta Biomater, 2016, 29:161-169.
15. LINDNER D, ZIETSCH C, TANK J, et al. Cardiac fibroblasts support cardiac inflammation in heart failure[J]. Basic Res Cardiol, 2014, 109(5):428.
16. KRIZAJ D, RYSKAMP D A, TIAN Ning, et al. From mechanosensitivity to inflammatory responses:new players in the pathology of glaucoma[J]. Curr Eye Res, 2014, 39(2):105-119.
17. AL M S, JOHNSON J R, HAMID Q. Remodeling in asthma[J]. Journal of Allergy and Clinical Immunology, 2011, 128:451-462.
18. DURRANI S R, VISWANATHAN R K, BUSSE W W. What effect does asthma treatment have on airway remodeling? Current perspectives[J]. J Allergy Clin Immunol, 2011, 128(3):439-448; quiz 449-50.
19. NILIUS B, DROOGMANS G, WONDERGEM R. Transient receptor potential channels in endothelium:solving the Calcium entry puzzle?[J]. Endothelium, 2003, 10(1):5-15.

Journal of Biomedical Engineering

Effects of Mechanical Stretch on Expression of Airway Remodeling Associated Factors in Human Bronchial Epithelioid Cells

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