The pathogenesis of pulmonary fibrosis: a moving target

Abstract

Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal lung architecture and finally death. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the delineation of primary pathways has proven to be elusive.In this review susceptibility and injurious agents, such as viruses and gastro-oesophageal reflux, and their probable role in initiating disease will be discussed. Further topics that are elaborated are candidate ancillary pathways, including immune mechanisms, oxidative and endoplasmic reticulum stress, activation of the coagulation cascade and the potential role of stem cells. This review will try to provide the reader with an integrated view on the current knowledge and attempts to provide a road map for future research.It is important to explore robust models of overall pathogenesis, reconciling a large number of clinical and scientific observations. We believe that the integration of current data into a ''big picture'' overview of fibrogenesis is essential for the development of effective antifibrotic strategies. The latter will probably consist of a combination of agents targeting a number of key pathways.

Rapamycin protects against paraquat‑induced pulmonary epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway

“…Aging, smoking and infection have been reported as risk factors for pulmonary fibrosis (11). The pathological characteristics of pulmonary fibrosis are repetitive microscopic alveolar epithelial cell injury, dysregulated repair, fibroblast proliferation and accumulation of extracellular matrix, which ultimately result in respiratory failure (12).…”

Disease stratification in idiopathic pulmonary fibrosis: the dawn of a new era?

“…As such, multiple cascades, all of which play a role in normal wound healing, are involved in the progressive fibro-proliferation that characterises IPF [3,4]. These abnormalities in wound healing-related mechanisms result in a myriad of growth factors, cytokines, chemokines and lipid mediators being differentially regulated in the lungs of patients with IPF [4]. This abnormal interplay of cell-cell interactions and signalling cascades is redolent of the abnormalities observed in cancer [5].…”

“…A growing body of evidence points to IPF arising as the consequence of an aberrant wound healing response occurring after repetitive alveolar injury in genetically susceptible individuals. As such, multiple cascades, all of which play a role in normal wound healing, are involved in the progressive fibro-proliferation that characterises IPF [3,4]. These abnormalities in wound healing-related mechanisms result in a myriad of growth factors, cytokines, chemokines and lipid mediators being differentially regulated in the lungs of patients with IPF [4].…”

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

“…Remarkable progress has been achieved over the past decade regarding the pathogenesis of this dismal disease [6,7]. Originally, IPF was considered an inflammation-driven process.…”