Smoking-Dependent Distal-to-Proximal Repatterning of the Adult Human Small Airway Epithelium

Abstract

Smoking-induced global distal-to-proximal reprogramming of the SAE represents a novel pathologic feature of COPD and is mediated by exaggerated epidermal growth factor/epidermal growth factor receptor signaling in SAE BCs.

Best of Milan 2017—ERS Lung Science Conference session “Lung tissue repair and remodeling in chronic lung diseases: mechanisms and therapeutic approaches”

“…A pathway analysis identified the EGF/EGFR signaling pathway as main regulator of the proximalization (P)-signature genes, which were also confirmed to be functionally relevant in in vitro exposures of primary airway epithelial cells to cigarette smoke extract (8). As these transcriptomic alterations were found in regions without histological abnormalities, the authors speculated that these events occur very early in the development of COPD (8). This study gives important insight in early mechanisms and effects of cigarette smoke on airway epithelial cells.…”

“…"proximalization" correlated with lung function (FEV 1 /FVC ratio), indicating functional consequences of those genomic alterations (8). A pathway analysis identified the EGF/EGFR signaling pathway as main regulator of the proximalization (P)-signature genes, which were also confirmed to be functionally relevant in in vitro exposures of primary airway epithelial cells to cigarette smoke extract (8).…”

“…To further investigate this, a recent study by Yang and colleagues analyzed the transcriptomic profiles of small airway epithelial cells, obtained by bronchoscopic brushing of 10 th -12 th generation bronchi (8). By comparing the expression profiles of large and small airway epithelium (SAE), the authors were able to develop a proximal-to-distal airway gene expression signature (8).…”

“…By comparing the expression profiles of large and small airway epithelium (SAE), the authors were able to develop a proximal-to-distal airway gene expression signature (8). Of note, the differences in expression were not simply due to a difference in cellular composition, but rather a distinct signature respective of the environment of e.g., ciliated cells (8).…”

“…By comparing the expression profiles of large and small airway epithelium (SAE), the authors were able to develop a proximal-to-distal airway gene expression signature (8). Of note, the differences in expression were not simply due to a difference in cellular composition, but rather a distinct signature respective of the environment of e.g., ciliated cells (8). In SAE of smokers with or without COPD, the distal signature was decreased, while the proximal genes were upregulated-an observation which the authors termed 'distal-to-proximal repatterning' (8).…”