Fibrosis in distinct tissues

The collection of articles in this special issue ofConnective Tissue Research brings to attention the complexity of fibrosis, the clinical challenges associated with excessive accumulation of fibrotic tissue, and the commercial effort to combat the problem. Regardless of the initial trauma or the anatomical site of injured tissue, inflammatory processes accelerate pathomechanisms of fibrosis. Specifically, inflammation releases various growth factors and cytokines that lead to the formation of fibrotic scar tissue. The excessive deposition of this tissue within or around injured organs alters their function, thereby causing disease, or, in some cases, death. The main component of the fibrotic deposits is a collagen-rich matrix, which forms when collagen molecules—most notably collagen I—assemble into collagen fibrils in response to tissue injury.When formed and crosslinked, the collagen fibrils are stable structures that alter mechanical, physiological, and biological functions of affected organs. Because of the crucial role of collagen, work to develop anti-fibrotic approaches has primarily focused on reducing its production. These efforts mostly target complex intracellular processes associatedwith accelerated collagen production. Despite this endeavor, antifibrotic treatments currently used in the clinic are mostly ineffective and frequently cause significant side effects. Recently, scientists have recognized the potential value of targeting the extracellular processes of fibrotic tissue formation. For instance, efforts have been made to inhibit collagen cross-linking by targeting one enzyme from the lysyl oxidase group that catalyzes cross-link formation. Moreover, when anti-collagen antibody was used to block collagen fibrillogenesis directly, the method limited arthrofibrosis in an animal model. Nevertheless, the clinical utility of the extracellular anti-fibrotic targets awaits further, more complete investigation. Developing anti-fibrotic approaches is challenging because the complex pathomechanisms of fibrosis interlace with the mechanisms of normal tissue repair and remodeling. The development of fully effective anti-fibrotic treatments will likely require directing attention at multiple targets. Furthermore, these treatments may need to be tailored in order to meet the challenges imposed by the specific anatomical locations in which fibrotic tissues appear. As fibrosis can cause failure of the lung, liver, or kidney that leads to death, organ fibrosis is the primary target of studies carried out at various academic and commercial research institutions. In this special issue of Connective Tissue Research, however, the authors draw attention to fibrotic changes occurring in other tissues. Specifically, the authors discuss fibrosis in peripheral nerves (1), tendons (2), joints (3), and in the gums (4). These tissues represent a varied group whose functions may be severely altered by the fibrotic changes. Other members of this group include cornea, vocal cords, muscle, and abdominal connective tissues, to name only a few. While the fibrotic changes occurring in those tissues are not necessarily lifethreatening, they present serious medical problems for which no effective treatments exist. This special issue also presents a review article describing oncostatin M and its potential role in fibrosis. In this article, the authors (5) not only discuss the potential mechanisms of action of oncostatin M, but also evaluate this cytokine as a potential anti-fibrotic target. Realizing the need for a more profound understanding of the pathomechanisms of idiopathic pulmonary fibrosis (IPF), Roque et al. (6) discuss novel concepts on the etiology of IPF. In their article, the authors discuss the possibility that, in IPF, the epithelial progenitor cells, as well as immune cells and fibroblasts, become functionally impaired due to the accumulation or loss of expression of various crucial proteins. Moreover, they propose that central to this defect is the dysregulation of the ubiquitin-proteasome system (UPS), which is the primary protein-degradation system in eukaryotic cells. Lastly, the authors discuss how targeting the UPS system could treat IPF and perhaps other fibrotic lung diseases as well. These articles not only broaden our knowledge on the pathomechanisms of fibrosis and indicate new anti-fibrotic targets, but