TY - JOUR
T1 - B-type natriuretic peptide and extracellular matrix protein interactions in human cardiac fibroblasts
AU - Huntley, Brenda K.
AU - Ichiki, Tomoko
AU - Sangaralingham, S. Jeson
AU - Chen, Horng H.
AU - Burnett, John C.
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
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U2 - 10.1002/jcp.22253
DO - 10.1002/jcp.22253
M3 - Article
C2 - 20506274
AN - SCOPUS:77956505986
SN - 0021-9541
VL - 225
SP - 251
EP - 255
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -