Macrophages regulate tissue regeneration following injury. They can worsen tissue injury by producing reactive oxygen species and other toxic mediators that disrupt cell metabolism, induce apoptosis, and exacerbate ischemic injury. However, they also produce a variety of growth factors, such as IGF-1, VEGF-α, TGF-β, and Wnt proteins that regulate epithelial and endothelial cell proliferation, myofibroblast activation, stem and tissue progenitor cell differentiation, and angiogenesis. Proresolving macrophages in turn restore tissue homeostasis by functioning as anti-inflammatory cells, and macrophage-derived matrix metalloproteinases regulate fibrin and collagen turnover. However, dysregulated macrophage function impairs wound healing and contributes to the development of fibrosis. Consequently, the mechanisms that regulate these different macrophage activation states have become active areas of research. In this review, we discuss the common and unique mechanisms by which macrophages instruct tissue repair in the liver, nervous system, heart, lung, skeletal muscle, and intestine and illustrate how macrophages might be exploited therapeutically.

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