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Cardiovascular & Hematological Disorders-Drug Targets
(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)
ISSN (Print): 1871-529X
ISSN (Online): 2212-4063
Epub Full Text Article
DOI: 10.2174/1871529X14666140505122510      Price:  $95









Transcriptional Control of Collagen I Gene Expression

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Author(s): P Roche and M P Czubryt
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 cisand 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
Keywords:
Collagen, extracellular matrix, gene expression, intron, promoter, transcription
Affiliation:
Department of Physiology, University of Manitoba and Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada