Fibrosis is the excessive deposition of extracellular matrix (ECM), mainly collagen, that replaces normal tissue after chronic injury or inflammation and can lead to organ failure in the lung, liver, kidney, heart and skin. Injury activates macrophages and other immune cells that release pro-fibrotic factors such as TGF-beta, PDGF, CTGF and IL-13. TGF-beta signaling through SMAD proteins drives fibroblasts to become contractile, ACTA2 positive myofibroblasts that produce collagens and fibronectin. Matrix remodeling is controlled by the balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).