Editorial

Treatment of idiopathic pulmonary fibrosis: the rise and fall of corticosteroids

This chapter is devoted to the description of morphological, clinical, and radiological features of idiopathic interstitial pneumonia (IIP). The main diagnostic features of IIP are defined, and each clinical type is described with a wide range of high-resolution computed tomography series, allowing visual comparison of closely related radiological patterns. For most common forms, descriptions of the alveoloscopic picture are provided. Differential diagnosis of IIP is often challenging, so key diagnostic points for similar diseases are discussed. Modern approaches for management of patients with IIP are also considered.

Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.

The paramount importance of the homeostasis of the extracellular matrix for pulmonary function is exemplified by two opposing extremes: emphysema and pulmonary fibrosis. This study examined the putative role of cathepsin K (catK) in the pathology of lung fibrosis in mice and its relevance to the human disease activity. We compared the induction of lung fibrosis by administration of bleomycin. CTSK^−/− mice deposited significantly more extracellular matrix than control mice. Primary lung fibroblasts derived from CTSK^−/− mice showed a decreased collagenolytic activity indicating the role of catK in collagen degradation. Interestingly, CTSK^+/+ control mice revealed an increased expression of catK in fibrotic lung regions suggesting a protective role of catK to counter the excessive deposition of collagen matrix in the diseased lung. Similarly, in lung specimens obtained from patients with lung fibrosis fibroblasts expressed larger amounts of catK than those obtained from normal lungs. Activation of human pulmonary fibroblasts in primary cell cultures led to an increased activity of catK through enhanced gene transcription and protein expression and to increased intracellular collagenolytic activity. We believe that this is the first study to show that catK plays a pivotal role in lung matrix homeostasis under physiological and pathological conditions.