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Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen\u2010producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial\/endothelial\u2010mesenchymal (EMT\/EndMT) transition, as well as from circulating fibroblast\u2010like cells called fibrocytes that are derived from bone\u2010marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen\u2010associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL\u201013, IL\u201021, TGF\u2010\u03b21), chemokines (MCP\u20101, MIP\u20101\u03b2), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator\u2010activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin\u2013angiotensin\u2013aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. 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