Canadian Contributions in Fibroblast Biology

Abstract

Fibroblasts are stromal cells found in virtually every tissue and organ of the body. For many years, these cells were often considered to be secondary in functional importance to parenchymal cells. Over the past 2 decades, focused research into the roles of fibroblasts has revealed important roles for these cells in the homeostasis of healthy tissue, and has demonstrated that activation of fibroblasts to myofibroblasts is a key step in disease initiation and progression in many tissues, with fibrosis now recognized as not only an outcome of disease, but also a central contributor to tissue dysfunction, particularly in the heart and lungs. With a growing understanding of both fibroblast and myofibroblast heterogeneity, and the deciphering of the humoral and mechanical cues that impact the phenotype of these cells, fibroblast biology is rapidly becoming a major focus in biomedical research. In this review, we provide an overview of fibroblast and myofibroblast biology, particularly in the heart, and including a discussion of pathophysiological processes such as fibrosis and scarring. We then discuss the central role of Canadian researchers in moving this field forwards, particularly in cardiac fibrosis, and highlight some of the major contributions of these individuals to our understanding of fibroblast and myofibroblast biology in health and disease.

Keywords: Canada; cell biology; fibroblast; fibrosis; metabolism; myofibroblast.

Figure 1

Homeostatic and pathological functions of fibroblasts (left) and myofibroblasts (right). Fibroblasts normally perform a number of key supportive roles in healthy tissues, and ideally contribute to the non-pathological healing of wounds. In response to physical and chemical signals, fibroblasts activate and undergo phenotypic conversion to myofibroblasts, altering their function. Persistence of myofibroblasts may lead to a failure to resolve repair processes such as wound healing, which in turn can lead to fibrosis and replacement of functional tissue with non-functional scar, can promote cellular transformation and metastasis in cancer, and can contribute to tissue aging. The negative impacts of fibroblast activation on tissue function can range from being relatively minor or cosmetic, to life-threatening.