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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• 作者：Qian Yu ; Minchao Li ; ^{liminc66@aliyun.com}
• 关键词：IL-13 ; interleukin-13 ; MMP-9 ; matrix metalloprotein-9 ; HBE ; human bronchial epithelioid ; TRPC1 ; transient receptor potential canonical 1 ; COPD ; chronic obstructive pulmonary disease ; PIP2 ; phosphatidylinositol-4 ; 5-bisphosphate ; PKC ; protein kinase C ; ATCC ; American Type Culture Collection ; EDTA ; Ethylene Diamine Tetraacetic Acid BAPTA-AM ; 1 ; 2-Bis(2-aminophenoxy)ethane-N ; N ; N&prime ; N&prime ; -tetraacetic acid tetrakis(acetoxymethyl ester) ; PVDF ; polyvinylidene fluoride ; SDS-PAGE ; sodium dodecyl su
• 刊名：Journal of Biomechanics
• 出版年：2017
• 出版时间：25 January 2017
• 年：2017
• 卷：51
• 期：Complete
• 页码：89-96
• 全文大小：2305 K
• 卷排序：51

文摘

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.