(760.1) Localizing the expression of Piezo2 in healthy and diseased lung tissue

Poster Board Number: E496

Lauren Hennis (Virginia Tech Carilion School of Medicine), Parker Hambright (Virginia Tech Carilion School of Medicine), Kristin Eden (Virginia Tech Carilion School of Medicine), Andrew Binks (Virginia Tech Carilion School of Medicine), Renee LeClair (Virginia Tech Carilion School of Medicine)

Intractable air hunger remains one of the most impactful symptoms of chronic cardiopulmonary disease and current pharmacological management remains limited. However, an endogenous mechanism for air hunger relief exists. Pulmonary stretch receptors (PSRs) responding to lung inflation reduce the brainstem drive to breathe and mitigate air hunger. Harnessing this mechanism could form the basis of a novel therapy.  Recent animal studies suggest Piezo2, a mechanically-gated cation channel, causes PSR depolarization when airway smooth muscle is stretched during inflation. We have assessed whether Piezo2 is associated with PSRs in healthy and diseased human airways to determine whether Piezo2 is a potential pharmaceutical target. 

Methods:

Human lung biopsies from NIH Lung Tissue Research Consortium were used for identification of Piezo2 receptors in emphysema, fibrosis, bronchiolitis, and normal lung tissue. Localization of Piezo2 was determined with immunofluorescent staining and imaged with confocal microscopy (Zeiss LSM880). As PSR fiber endings are associated with airway smooth muscle, co-staining for Smooth Muscle Antibody (SMA) and Calcitonin Gene-Related Peptide (CGRP) was performed to determine whether Piezo2 is associated with PSR.

Summary of results:

Piezo2 is associated with airway smooth muscle (as evidenced by SMA, figure 1) and neuroepithelial bodies in normal human lung tissue (evidenced by cGRP, figure 2) and expression persisted in all disease states tested.

Conclusions:  

Piezo2 location is consistent with that of PSR in human lungs, making it a candidate for the mechanoreceptive transducer of human PSRs as has been demonstrated in animal studies. Expression persists in disease, making Piezo2 a potential therapeutic target, but it is still yet to be determined if Piezo2 is more significantly associated with airway or vascular smooth muscle in different disease states. 

Support or Funding Information

Internal Funding





Figure 1:  Localization of Piezo2 with anti-SMA in normal lung, bronchiolitis, and emphysema colocalized with smooth muscle.; Figure 2:  Localization of Piezo2 with anti-cGRP in bronchiolitis and fibrosis. Bronchiolitis there is co-staining for anti-cGRP and anti-Piezo2 (arrow). Fibrosis: anti-cGRP only (top arrow) and co-staining for anti-cGRP and anti-piezo2 (bottom arrow)