title: B-type natriuretic peptide and extracellular matrix protein interactions in human cardiac fibroblasts.
abstract: Cardiac fibroblasts (CFs) regulate myocardial remodeling by proliferating, differentiating, and secreting extracellular matrix (ECM) proteins. B-type natriuretic peptide (BNP) is anti-fibrotic, inhibits collagen production, augments matrix metalloproteinases, and suppresses CF proliferation. Recently, we demonstrated that the ECM protein fibronectin (FN) augmented production of BNP's second messenger, 3', 5' cyclic guanosine monophosphate (cGMP) in CFs, supporting crosstalk between FN, BNP, and its receptor, natriuretic peptide receptor A (NPR-A). Here, we address the specificity of FN to augment cGMP generation by investigating other matrix proteins, including collagen IV which contains RGD motifs and collagen I and poly-L-lysine, which have no RGD domain. Collagen IV showed increased cGMP generation to BNP similar to FN. Collagen I and poly-L-lysine had no effect. As FN also interacts with integrins, we then examined the effect of integrin receptor antibody blockade on BNP-mediated cGMP production. On FN plates, antibodies blocking RGD-binding domains of several integrin subtypes had little effect, while a non-RGD domain interfering integrin alphavbeta3 antibody augmented cGMP production. Further, on uncoated plates, integrin alphavbeta3 blockade continued to potentiate the BNP/cGMP response. These studies suggest that both RGD containing ECM proteins and integrins may interact with BNP/NPR-A to modulate cGMP generation.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Disease, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. huntley.brenda@mayo.edu
authors.forename: Brenda K
authors.initials: BK
authors.lastname: Huntley
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichiki
authors.forename: S Jeson
authors.initials: SJ
authors.lastname: Sangaralingham
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D020097:Natriuretic Peptide, Brain; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP