Putting the Squeeze on Airway Epithelia

Abstract

Asthma is characterized by chronic inflammation, airway hyperresponsiveness, and progressive airway remodeling. The airway epithelium is known to play a critical role in the initiation and perpetuation of these processes. Here, we review how excessive epithelial stress generated by bronchoconstriction is sufficient to induce airway remodeling, even in the absence of inflammatory cells.

FIGURE 1.

Schematic diagram of the in vitro compressive system A transepithelial air-pressure gradient at a magnitude of 30 cmH₂O is applied to primary human bronchial epithelial cells maintained in an air-liquid interface culture. Reprinted from Ref. , with permission from Annu Rev Physiol.

FIGURE 2.

Collagen deposition and goblet cell hyperplasia in response to compressive stress A: the application of compressive stress significantly induces collagen type III production from fibroblasts in basolateral conditioned media collected from human bronchial epithelial cells. Reprinted from Ref. , with permission from the National Academy of Sciences (Copyright 2001). B: the application of chronic intermittent compressive stress induces goblet-cell hyperplasia in human bronchial epithelial cells. Reprinted from Ref. , with permission from the American Thoracic Society (Copyright 2015).

FIGURE 3.

Collagen deposition and goblet cell hyperplasia in response to bronchoconstriction in patients with mild asthma A and B: immunohistochemical staining of collagen type III is shown in brown before (A) and after (B) methacholine challenges. C and D: periodic acid-Schiff staining of goblet cells is shown in purple before (C) and after (D) methacholine challenges. Scale bar represents 30 μm. Reprinted frome Ref. , with permission from the N Engl J Med.

FIGURE 4.

A jamming phase diagram for the collective migration of the cellular monolayer In the cellular monolayer, the transition between a jammed (solid-like) state and an unjammed (fluid-like) state might be governed by a jamming phase diagram. Reprinted from Ref. , with permission from Differentiation.