title: Role of caveolin-1 in fibrotic diseases.
abstract: Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic potential of an integral membrane protein, caveolin-1. While caveolin-1 has been widely studied for its role in the regulation of cell signaling and endocytosis, its possible implication in fibrosis remains largely unclear. In this review we survey involvement of caveolin-1 in various cellular processes and highlight different aspects of its antifibrotic activity. We hypothesize that caveolin-1 conveys a homeostatic function in the process of fibrosis by (a) regulating TGF-β1 and its downstream signaling; (b) regulating critical cellular processes involved in tissue repair, such as migration, adhesion and cellular response to mechanical stress; and (c) antagonizing profibrotic processes, such as proliferation. Finally, we consider this homeostatic function of caveolin-1 as a possible novel approach in treatment of fibroproliferative diseases.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Gvaramia
authors.forename: Marjolein E
authors.initials: ME
authors.lastname: Blaauboer
authors.forename: Roeland
authors.initials: R
authors.lastname: Hanemaaijer
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D040542:Mechanotransduction, Cellular; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D053773:Transforming Growth Factor beta1
keywords: CSD; CSD peptide; Caveolin-1; ECM; EGFR; FAK; Fibrosis; IPF; MEF; Matrix remodeling; Mechanotransduction; TGF-β type I receptor; TGF-β type II receptor; TGF-β1; TGFβRI; TGFβRII; caveolin scaffolding domain; epidermal growth factor receptor; extracellular matrix; focal adhesion kinase; idiopathic pulmonary fibrosis; mouse embryonic fibroblasts; pY14-Cav1; phospho-caveolin; α-smooth muscle actin; αSMA