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Transforming growth factor \u03b21 (TGF-\u03b21) is one of the most powerful profibrotic cytokines. Thus, blocking TGF-\u03b21 activity by natural inhibitors represents a valid and logical strategy to combat hepatic fibrosis. One of the natural inhibitors of TGF-\u03b21 is decorin, a small leucine-rich proteoglycan that binds with high affinity to this cytokine and prevents its interaction with pro-fibrotic receptors. Recent evidence has shown that decorin has a protective role in liver fibrogenesis insofar as its genetic ablation in mice leads to enhanced matrix deposition, impaired matrix degradation, and \u201cactivation\u201d of hepatic stellate cells, the main producers of fibrotic tissue. Moreover, TGF-\u03b21 exerts a stronger effect when functional decorin is absent. These data provide robust genetic evidence for a direct role of endogenous decorin in preventing and retarding hepatic fibrosis. 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