TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene expression.
The balance between production and degradation of type I collagen plays a critical role in the development and maintenance of organ and tissue integrity. It also represents the most crucial element governing the process of tissue repair. The synthesis of type I collagen gene is highly regulated by different cytokines at the transcriptional level. Especially, transforming growth factor beta (TGF-beta), a key player in the physiopathology of tissue repair, enhances type I collagen gene expression. In contrast, tumor necrosis factor alpha (TNF-alpha), whose matrix-remodelling function is opposite to that of TGF-beta, reduces type I collagen gene expression. This review focuses on transcriptional regulation of type I collagen by TGF-beta and TNF-alpha and on the molecular mechanisms that control the antagonistic activity of TNF-alpha against TGF-beta-driven type I collagen gene expression.
Verrecchia
Franck
F
INSERM U532, Institut de Recherche sur la Peau, Pavillon Bazin, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Mauviel
Alain
A
D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
D024042:Collagen Type I; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha