Factors involved in the regulation of type I collagen gene expression: implication in fibrosis.
Type I collagen, the major component of extracellular matrix in skin and other tissues, is a heterotrimer of two alpha1 and one alpha2 collagen polypeptides. The synthesis of both chains is highly regulated by different cytokines at the transcriptional level. Excessive synthesis and deposition of collagen in the dermal region causes thick and hard skin, a clinical manifestation of scleroderma. To better understand the causes of scleroderma or other tissue fibrosis, it is very important to investigate the molecular mechanisms that cause upregulation of the Type I collagen synthesis in these tissues. Several cis-acting regulatory elements and trans-acting protein factors, which are involved in basal as well as cytokine-modulated Type I collagen gene expression, have been identified and characterized. Hypertranscription of Type I collagen in scleroderma skin fibroblasts may be due to abnormal activities of different positive or negative transcription factors in response to different abnormally induced signaling pathways. In this review, I discuss the present day understanding about the involvement of different factors in the regulation of basal as well as cytokine-modulated Type I collagen gene expression and its implication in scleroderma research.
Ghosh
Asish K
AK
Section of Rheumatology, Department of Medicine, 1158 Molecular Biology Research Building, University of Illinois, 900 South Ashland Avenue, Chicago, IL 60607, USA. Ghoshak@uic.edu
D000818:Animals; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D024042:Collagen Type I; D016207:Cytokines; D004268:DNA-Binding Proteins; D014157:Transcription Factors