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B‐type natriuretic peptide and extracellular matrix protein interactions in human cardiac fibroblasts
Author(s) -
Huntley Brenda K.,
Ichiki Tomoko,
Sangaralingham S. Jeson,
Chen Horng H.,
Burnett John C.
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22253
Subject(s) - fibronectin , integrin , extracellular matrix , cyclic guanosine monophosphate , natriuretic peptide , collagen receptor , chemistry , microbiology and biotechnology , receptor , type i collagen , npr2 , medicine , endocrinology , biochemistry , biology , heart failure , nitric oxide , organic chemistry
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 αvβ3 antibody augmented cGMP production. Further, on uncoated plates, integrin αvβ3 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. J. Cell. Physiol. 225: 251–255, 2010. © 2010 Wiley‐Liss, Inc.