For decades we have known that the overgrowth, hardening and scarring of tissues (so-called fibrosis) represents the final common pathway and best histological predictor of disease progression in most organs. Fibrosis is the culmination of both excess extracellular matrix deposition due to ongoing or severe injury, and a failure to regenerate. An inadequate wound repair process ultimately results in organ failure through a loss of function, and is therefore a major cause of morbidity and mortality in disease affecting both multiple and individual organs. Whilst the pathology of fibrosis and its significance are well understood, until recently we have known little about its molecular regulation. Current therapies are often indirect and non-specific, and only slow progression by a matter of months. The recent identification of novel therapeutic targets, and the development of new treatment strategies based on them, offers the exciting prospect of more efficacious therapies to treat this debilitating disorder. This Research Topic therefore compromises several up-to-date mini-reviews on currently known and emerging therapeutic targets for fibrosis including: the Transforming Growth Factor (TGF)-family; epigenetic factors; Angiotensin II type 2 (AT2) receptors; mineralocorticoid receptors; adenosine receptors; caveolins; and the sphingosine kinase/sphingosine 1-phosphate and notch signaling pathways. In each case, mechanistic insights into how each of these factors contribute to regulating fibrosis progression are described, along with how they can be targeted (by existing drugs, small molecules or other mimetics) to prevent and/or reverse fibrosis and its contribution to tissue dysfunction and failure. Two additional reviews will discuss various anti-fibrotic therapies that have demonstrated efficacy at the experimental level, but are not yet clinically approved; and the therapeutic potential vs limitations of stem cell-based therapies for reducing fibrosis while facilitating tissue repair. Finally, this Research Topic concludes with a clinical perspective of various anti-fibrotic therapies for cardiovascular disease (CVD), outlining limitations of currently used therapies, the pipeline of anti-fibrotics for CVD and why so many anti-fibrotic drugs have failed at the clinical level.

Rare diseases collectively affect millions of Americans of all ages, but developing drugs and medical devices to prevent, diagnose, and treat these conditions is challenging. The Institute of Medicine (IOM) recommends implementing an integrated national strategy to promote rare diseases research and product development.

Fibroproliferative diseases are a broad spectrum of entities from organ-specific involvement (e.g., pulmonary, heart, liver, and kidney fibrosis) to multi-system diseases such as systemic sclerosis and sclerodermatous graft vs. host disease. These diseases also encompass pathophysiologies not readily recognizably related, such as macular degeneration and cancer metastasis. Fibroproliferative diseases are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Remarkable progress in elucidating the pathogenesis of these common diseases with fibrotic components, including the critical roles of myofibroblasts and the molecular mechanisms driving the transcriptional activation involved in the induction of fibrosis. As the importance of these processes is realized in the long-term recovery and treatment of diseases, effective anti-fibrotic therapies targeting the underlying ongoing disease processes are lacking. The complexity of discovering and applying therapies to fibroproliferative disease may be due to the diversity of the systems the pathogenesis of disease itself involves. By nature, fibroproliferative diseases are interdisciplinary, involving multiple cell types (organ-specific epithelial cells), immune cells, endothelial cells, and fibroblasts. Bone marrow, cytokines, and organ-specific pathologies further speckle both the clinical and scientific disciplines in such a way that communication is often limited to the clinical or scientific tribes we live in, despite the greatest access to information known to man available today. Therefore, the primary focus of this text is to bring together authors from a diversity of both clinical, scientific, and therapeutic backgrounds for readers to more fully appreciate that fantastic platform that is available to build upon to lessen the isolation of the clinical and scientific disciplines. With advances in the discovery of pre-clinical therapeutic targets (at least 20+ to date) involving TGF-beta (and other cytokines), transcription factors, and downstream kinases, it’s important to both recognize the broader impact and potential opportunities that exist even today. This book will serve as a state-of-the-art resource for physicians and translational medical researchers alike who are interested in the rapidly evolving field of fibroproliferative diseases. The book will provide new insight into the fundamental mechanisms of classic fibrotic pathophysiologic processes like myocardial infarction, idiopathic pulmonary fibrosis, chronic kidney disease, wound healing, and systemic sclerosis. It will also highlight the many new areas of therapeutic investigation currently underway. Lastly, we will touch upon newly emerging fields investigating the role of fibrosis in macular degeneration and cancer metastasis. The chapters will be written by established experts in their fields, including clinicians (cardiologists, cardiovascular surgeons, pathologists, and general practitioners) and translational biomedical researchers in a wide range of disciplines. However, the material will certainly have a broader audience including medical residents, fellows, and general practitioners as well as M.D. or Ph.D. post-doctoral research fellows. While comprehensive, we'll attempt to present the material in a manner that simplifies the complex pathophysiologic mechanisms that underlie common fibroproliferative diseases while making it appealing to a broad audience.

This unique book deals with both inflammation and cancer in a single source of publication. They are seldom grouped together although it has been known that both diseases are closely associated, particularly in the gastrointestinal tract and liver. As the book touches on two such major areas of diseases in humans, it should be of interest to a wider audience of researchers and readers. It is noted that the book combines the effort of both basic scientists and clinicians from different countries with extensive experiences in molecular biology and clinical practice to unveil the most updated picture of the pathogenesis and therapeutic strategies in the treatment of inflammation and cancer in the digestive tract. In this regard, potential pathogenic modulators and also therapeutic options are widely discussed. These types of information would definitely broaden our knowledge in better understanding these diseases.