Cytokine modulation of extracellular matrix gene expression: relevance to fibrotic skin diseases.
Fibrotic skin diseases demonstrate a spectrum of phenotypic manifestations with a unifying histopathologic hallmark, i.e. the accumulation of collagen in the lesional skin. Mechanistically, collagen deposition could result either from enhanced biosynthetic activity or reduced rate of degradation, thus leading to an imbalance in physiological turnover of collagen in the dermis. This overview summarizes the mechanisms of regulation of collagen gene expression in fibroblasts as exemplified by cytokine modulation. This summary also provides evidence in support of the notion that transcriptional activation of collagen gene expression is the underlying mechanism leading to development of fibrotic cutaneous lesions, as documented in keloids, a prototypic example of cutaneous fibrosis.
Uitto
J
J
Department of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. jouni.uitto@mail.tju.edu
Kouba
D
D
D000818:Animals; D003094:Collagen / Q000235:genetics; D016207:Cytokines / Q000502:physiology*; D005109:Extracellular Matrix / Q000235:genetics*; D005355:Fibrosis / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D012871:Skin Diseases / Q000235:genetics* / Q000503:physiopathology
D016207:Cytokines; D003094:Collagen