Organ fibrosis: beyond collagen I expression. Fibroblast phenotype and basement membrane proteins

The prevalence of fibrotic disease and its contribution to organ failure have wide-ranging consequences in terms of both morbidity and mortality and are particularly relevant in chronic conditions that afflict aging populations. The paucity of treatment options for those with fibrosis-dependent complications illustrates the challenge and underlying complexity of controlling and reducing extracellular matrix (ECM) content once fibrosis has been established. Legitimately, a major focus of research in fibrosis has centered on transcriptional regulation of fibrillar collagen, particularly collagen I, and factors that induce the expression of genes encoding the fibrillar collagens. However, knowledge that other facets of extracellular matrix biology, in addition to fibrillar collagen content, also make significant contributions to fibrosis is appreciated with emerging significance. Herein, a summary of some recent advances in uncovering critical fibroblast activation states, ECM organization, and composition of fibrotic ECM, including basement membrane components, is discussed. In addition, evidence in support of distinct fibroblast phenotypes in fibrotic tissues, which once established, limit regression of fibrosis despite alleviation of the initiating pathology, is given. As the capacity to reduce established fibrosis has the potential for profound translational significance across organs, more research into each of these important processes is merited.