Background: The lung is a mechanosensitive organ, where cells experience a range of mechanical forces. Chronic obstructive pulmonary disease (COPD) involves abnormal macroscopic and cellular changes that impact the mechanical properties of the lung and the extracellular matrix (ECM). The Piezo (PZ) family - PZ1/2, are mechanosensitive channels expressed, among others, on airway smooth muscle (ASM) that mediate cellular responses to stretch and ECM biomechanics. The role and expression of PZs in COPD lung ASM is not known. We hypothesize that PZ expression, regulation and activation is altered in COPD lung ASM and involved in ECM regulation.

Methods: Distribution and expression of PZ proteins in lung tissue was assessed using IHC comparing COPD stage IV to control (n=10/group). The area and intensity of staining ASM was quantified using ImageJ. Isolated ASM cells from control and COPD stage II and IV (n=6) patients were exposed to the PZ1 agonist Yoda1 and/or stretch for 24h, followed by measuring gene and protein expression of PZs and ECM genes.

Results: Area and intensity of PZ1 and PZ2 staining was higher in COPD IV ASM compared to control. Gene expression of PZ1 increased upon stretching in control but not in COPD ASM cells, while PZ2 protein expression decreased upon stretching in combined groups. Yoda1 treatment resulted in decreased Collagen1, fibulin1 and periostin gene expression in ASM cells of the combined groups.

Conclusion: Higher PZs expression in COPD lung ASM together with altered PZ response to stretching and decreased ECM gene expression upon PZ activation, supports a potential role for PZ activation in abnormal ECM-ASM crosstalk in COPD.