title: Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor beta.
abstract: Understanding the impact of extracellular matrix sub-types and mechanical stretch on cardiac fibroblast activity is required to help unravel the pathophysiology of myocardial fibrotic diseases. Therefore, the purpose of this study was to investigate pro-fibrotic responses of primary human cardiac fibroblast cells exposed to different extracellular matrix components, including collagen sub-types I, III, IV, VI and laminin. The impact of mechanical cyclical stretch and treatment with transforming growth factor beta 1 (TGFβ1) on collagen 1, collagen 3 and alpha smooth muscle actin mRNA expression on different matrices was assessed using quantitative real-time PCR. Our results revealed that all of the matrices studied not only affected the expression of pro-fibrotic genes in primary human cardiac fibroblast cells at rest but also affected their response to TGFβ1. In addition, differential cellular responses to mechanical cyclical stretch were observed depending on the type of matrix the cells were adhered to. These findings may give insight into the impact of selective pathological deposition of extracellular matrix proteins within different disease states and how these could impact the fibrotic environment.
authors.affiliation: School of Medicine & Medical Science, UCD Conway Institute, University College Dublin , Ireland and.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Watson
authors.forename: Dermot
authors.initials: D
authors.lastname: Phelan
authors.forename: Patrick
authors.initials: P
authors.lastname: Collier
authors.forename: Stephen
authors.initials: S
authors.lastname: Horgan
authors.forename: Nadia
authors.initials: N
authors.lastname: Glezeva
authors.forename: Gordon
authors.initials: G
authors.lastname: Cooke
authors.forename: Maojia
authors.initials: M
authors.lastname: Xu
authors.forename: Mark
authors.initials: M
authors.lastname: Ledwidge
authors.forename: Kenneth
authors.initials: K
authors.lastname: McDonald
authors.forename: John A
authors.initials: JA
authors.lastname: Baugh
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D007797:Laminin; D016212:Transforming Growth Factor beta; D003094:Collagen