Metalloproteinases in idiopathic pulmonary fibrosis

Abstract

In this article, we outline the current state of knowledge about the balance between collagen production and degradation in idiopathic pulmonary fibrosis (IPF). The dysregulated action of metalloproteinases implicated in IPF may play a central role in IPF pathogenesis. Inhibiting metalloproteinases in IPF may, therefore, have therapeutic potential, but our knowledge of their pathophysiological role is held back by limited animal models and the lack of specific inhibitors.

Mechanisms of Lung Fibrosis Resolution

“…28 These studies and others now demonstrate that the MMPs and TIMPs influence several cellular processes, including proliferation, survival, and inflammation, that directly or indirectly influence myofibroblast activation and ECM turnover. 23,24,29,30 Cross-linking of collagen and elastin are posttranslational modifications of the ECM that can hinder fibrosis resolution by preventing extracellular proteolytic enzymes from accessing binding sites. One family of enzymes mediating this cross-linking is lysyl oxidase and its homologues (lysyl oxidaseelike enzymes 1 to 4).…”

Improving care for patients with idiopathic pulmonary fibrosis (IPF) in the UK: a round table discussion

“…The pathophysiology of IPF is complex involving fibroproliferation, 2 epithelial cell apoptosis, 25 epithelial-mesenchymal transition, 26 neo-angiogenesis, 27 and intra-alveolar coagulopathy. As with most effective lung disease treatments, it is unrealistic for us to expect a single magic bullet to be universally effective.…”

The pathogenesis of pulmonary fibrosis: a moving target

“…Many genes significantly increased in fibrotic lungs encode proteins associated with ECM formation and degradation and proteins expressed by smooth muscle cells, including matrilysin, matrix metalloproteinase (MMP)7 [43], which is a metalloproteinase mediator of pulmonary fibrosis. It has become clear that MMPs exert pleiotropic effects, including proteolytic degradation of the ECM and in the processing of chemokines, cytokines and growth factors [44]. It might even be possible that enhanced MMP activity is, therefore, a mechanistic driver of progressive fibrosis in IPF.…”