机械转化
细胞外基质
纤维连接蛋白
成纤维细胞
细胞生物学
化学
背景(考古学)
MAPK/ERK通路
信号转导
生物
体外
生物化学
古生物学
作者
Mengning Zheng,Yang Yao,Niyati A. Borkar,Michael A. Thompson,Emily Zhang,Li Y. Drake,Xianwei Ye,Elizabeth R. Vogel,Christina M. Pabelick,Y. S. Prakash
出处
期刊:American Journal of Physiology-lung Cellular and Molecular Physiology
[American Physiological Society]
日期:2024-08-27
标识
DOI:10.1152/ajplung.00356.2023
摘要
Bronchial airways and lung parenchyma undergo both static and dynamic stretch in response to normal breathing but also in the context of insults such as mechanical ventilation (MV) or in diseases such as asthma and COPD which lead to airway remodeling involving increased extracellular matrix (ECM) production. Here, the role of fibroblasts is critical, but the relationship between stretch and fibroblast induced ECM remodeling under these conditions is not well-explored. Piezo (PZ) channels play a role in mechanotransduction in many cell and organ systems, but their role in mechanical stretch-induced airway remodeling is not known. To explore this, we exposed human lung fibroblasts to 10% static stretch on a background of 5% oscillations for 48 hours, with no static stretch considered controls. Collagen I, Fibronectin, α-SMA, and Piezo 1 (PZ1) expression were determined in the presence or absence of Yoda1 (PZ1 agonist) or GsMTx4 (PZ1 inhibitor). Collagen I, Fibronectin, and α-SMA expression was increased by stretch and Yoda1 while pretreatment with GsMTx4 or knockdown of PZ1 by siRNA blunted this effect. Acute stretch in the presence and absence of Yoda1 demonstrated activation of ERK pathway but not Smad. Measurement of [Ca 2+ ] i responses to histamine showed significantly greater responses following stretch: effects that were blunted by knockdown of PZ1.Our findings identify an essential role for PZ1 in mechanical stretch-induced production of ECM mediated by ERK phosphorylation and Ca 2+ influx in lung fibroblasts. Targeting PZ channels in fibroblasts may constitute a novel approach to ameliorate airway remodeling by decreasing ECM deposition.
科研通智能强力驱动
Strongly Powered by AbleSci AI