Effects of transient receptor potential canonical 1 (TRPC1) on the mechanical stretch-induced expression of airway remodeling-associated factors in human bronchial epithelioid cells |
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Affiliation: | 1. Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile;2. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile;3. Obstetrics and Gynecology Department, University of Chile Clinical Hospital, Santiago, Chile;4. Pathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile;1. Department of Ophthalmology & Visual Science, University of Utah School of Medicine and John Moran Eye Center, Salt Lake City, Utah;2. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah;3. Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina;4. Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York |
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Abstract: | Research has shown that mechanical stress stimulation can cause airway remodeling. We investigate the effects of mechanical stretch on the expression of the airway remodeling-associated factors interleukin-13 (IL-13) and matrix metalloprotein-9 (MMP-9) and signaling pathways in human bronchial epithelioid (16HBE) cells under mechanical stretch. A Flexcell FX-4000 Tension System with a flexible substrate was applied to stretch 16HBE cells at a 15% elongation amplitude and 1 Hz frequency, with stretching for 0.5 h, 1 h, 1.5 h and 2 h. The experimental group with higher IL-13, MMP-9, and TRPC1 expression and higher Ca2+ levels was selected for performing intervention experiment. These cells were pretreated with the transient receptor potential canonical 1 (TRPC1) channel antagonist SKF96365 and TRPC1-specific siRNA, and then mechanical stretch was applied. Our results provided evidences that mechanical pressure significantly increased IL-13, MMP-9, and TRPC1 protein and mRNA expression levels and intracellular Ca2+ fluorescence intensity at 4 time points compared with the control group. The peak IL-13, MMP-9, and TRPC1 expression levels were observed at 0.5 h after exposure to mechanical pressure. IL-13 and MMP-9 expression levels and Ca2+ fluorescence intensity in the stretch+SKF96365 group and in the stretch+TRPC1 siRNA group were significantly lower than those were in the mechanical stretch group. By incubating the cells with the intracellular calcium chelator BAPTA-AM, the expression of IL-13 and MMP9 was significantly decreased, and the expression level of TRPC1 remained unchanged. These observations suggest that mechanical stretch may induce an influx of Ca2+ and up-regulation of IL-13 and MMP-9 expression in 16HBE cells via activation of TRPC1. |
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Keywords: | Mechanical stretch Human bronchial epithelioid cells Interleukin-13 Matrix metalloprotein-9 Transient receptor potential canonical 1 |
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