title: Molecular aspects of regulation of collagen gene expression in fibrosis.
abstract: Fibrosis, the hyper-accumulation of scar tissue, is characterized by the overproduction and deposition of type I and III collagen by fibroblasts and is the one of the main pathologic outcomes of the autoimmune disorder scleroderma. While the causes of fibrosis in scleroderma are unknown, cytokines such as TGF-beta, IL-4 and IL-13, play a crucial role in the stimulation of collagen production have been implicated in the disease process. In fibroblasts stimulation of collagen production by these cytokines is dependent on the Smad and STAT6 signaling pathways induced by TGF-beta and IL-4, IL-13 respectively. Furthermore, mounting evidence suggest cytokine crosstalk is relevant in the sclerotic process. Our laboratory demonstrated an increase in TGF-beta1 gene transcription from fibroblasts stimulated with IL-4. In addition, TSK/+ mice lacking the IL-4alpha receptor show impaired transcription of the TGF-beta1 gene and did not display fibrosis. Likewise, it appears that STAT6 plays a role in fibroblast TGF-beta1 transcription after IL-4 or IL-13 stimulation. These findings suggest that an epistatic interaction between IL-4 and TGF-beta may exist which is crucial for pathologic sclerotic activity.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Rashpal K
authors.initials: RK
authors.lastname: Bhogal
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Stoica
authors.forename: Tracy L
authors.initials: TL
authors.lastname: McGaha
authors.forename: Constantin A
authors.initials: CA
authors.lastname: Bona
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D003094:Collagen