Epithelial-Mesenchymal Transition Contributes to Pulmonary Fibrosis via Aberrant Epithelial/Fibroblastic Cross-Talk

Charlotte Hill,Yihua Wang,Mark Jones,Donna Davies

doi:10.29245/2689-999x/2019/2.1149

Abstract

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic interstitial lung disease. Median survival is only 3 years, and treatment options are limited. IPF is thought to be a result of a combination of genetic and environmental factors with repetitive micro-injuries to alveolar epithelial cells playing a central role. IPF is characterised by aberrant extra cellular matrix (ECM) deposition by activated myofibroblasts. Epithelial-mesenchymal transition (EMT) is a process where polarised epithelial cells undergo molecular changes allowing them to gain a mesenchymal phenotype, with a subsequent enhanced ability to produce ECM components and increased migration and/or invasion. The source of myofibroblasts in IPF has been debated for many years, and EMT has been proposed as a source of these cells. However, lineage tracing in transgenic mice suggests the contribution of epithelial cells, which have undergone EMT, to the fibroblast population may be negligible. Instead, recent findings suggest that alveolar epithelial type II (ATII) cells undergoing EMT promote a pro-fibrotic microenvironment through paracrine signalling activating local fibroblasts. This review paper explores the contribution of ATII cells, which have undergone EMT, in the context of pulmonary fibrosis.

Highlights

Introduction and DiscussionIdiopathic pulmonary fibrosis (IPF)IPF is a chronic, progressive and fibrotic lung disease of unknown cause, which typically occurs in older adults
Recent findings suggest that alveolar epithelial type II (ATII) cells undergoing Epithelial-mesenchymal transition (EMT) promote a pro-fibrotic microenvironment through paracrine signalling activating local fibroblasts
Alveolar architecture is destroyed and healthy tissue is replaced by altered extra cellular matrix (ECM), with progressive dyspnoea and impairment of lung function leading to death[1,2]

Summary

Introduction

Introduction and DiscussionIdiopathic pulmonary fibrosis (IPF)IPF is a chronic, progressive and fibrotic lung disease of unknown cause, which typically occurs in older adults. Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic interstitial lung disease. IPF is thought to be a result of a combination of genetic and environmental factors with repetitive micro-injuries to alveolar epithelial cells playing a central role.

Results

Conclusion