title: Transcriptional control of collagen I gene expression.
abstract: Cardiac fibrosis is the pathological remodeling of the extracellular matrix (ECM) in response to stresses such as pressure overload or injury. While initially adaptive, myocardial remodeling and subsequent fibrosis causes increased wall stiffness, arrhythmias, cardiac dysfunction, and eventually heart failure. Though the disease processes and origins may differ, excess deposition of fibrillar collagens type I and III characterizes fibrosis in the heart, lungs, kidneys, liver, and skin. Under normal physiological conditions, high tensile strength collagen fibers maintain cardiac structural integrity, connect individual cardiomyocytes, transmit contractile force, and resist deformation and rupture of the ventricle during systole. Various factors contribute to the development of fibrosis by altering expression of ECM genes, including increased synthesis of pro-inflammatory cytokines, alterations in the levels of circulating hormones, and mechanical strain resulting from ECM degradation. This review focuses on the transcriptional mechanisms governing expression of the major cardiac collagen, type I. Key cis- and trans-acting regulators of collagen I gene expression are discussed. Surprisingly, relatively few transcriptional regulators of collagen synthesis have been identified specifically in cardiac fibroblasts. However, key players have been identified in other tissue and cell types, and are important to consider in elucidating the molecular mechanisms underpinning collagen gene expression in the heart in both health and disease.
authors.forename: Patricia
authors.initials: P
authors.lastname: Roche
authors.affiliation: Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6. mczubryt@sbrc.ca.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czubryt
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics*; D005109:Extracellular Matrix / Q000235:genetics / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D007438:Introns; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D024042:Collagen Type I