Tissue fibrosis is most often referred to in its pathological context and is a major cause of progressive organ failure and death. Here, we consider fibrosis as an evolutionarily conserved, adaptive tissue response to injury. The role of NADPH oxidase 4 (Nox4) as a novel pro-fibrogenic mediator is highlighted. The concept that Nox4 may function as an antagonistically pleiotropic gene in age-associated fibrotic disorders is discussed.
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