Mechanotherapeutics for the Treatment of Idiopathic Pulmonary Fibrosis
Hongwei Han 1, David Lagares 1
1 Department of Medicine, Division of Pulmonary and Critical Care Medicine; Fibrosis Research Center; Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology. Massachusetts General Hospital, Harvard Medical School, Boston, USA
*Correspondence: David Lagares, Email not available
Abstract
Idiopathic pulmonary fibrosis (IPF) is an age-related progressive lung disease characterized by excessive deposition of extracellular matrix (ECM) produced by activated myofibroblasts. Traditionally, myofibroblast activation has been thought to be exclusively driven by soluble biochemical stimuli, such as pro-fibrotic growth factors and cytokines. However, the mechanical properties of the fibrotic ECM including matrix stiffness have recently gained more attention given its ability to drive myofibroblast activation independently from soluble mediators. The study of fibroblast mechanobiology is an active area of research in IPF and focuses on understanding how matrix stiffness is sensed and translated into biochemical signaling via the so-called mechanotransduction pathways, which ultimately regulate profibrotic gene expression, ECM synthesis and myofibroblast survival. Here, we summarize the molecular mechanisms promoting mechano-activation of myofibroblasts in lung fibrosis and the potential of treating IPF with “mechanotherapeutics”, a novel class of anti-fibrotic therapeutic agents.
