B-type natriuretic peptide and extracellular matrix protein interactions in human cardiac fibroblasts

Brenda K. Huntley, Tomoko Ichiki, S Jeson Sangaralingham, Horng Haur Chen, John C Jr. Burnett

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)251-255
Number of pages5
JournalJournal of Cellular Physiology
Volume225
Issue number1
DOIs
StatePublished - Oct 2010

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Extracellular Matrix Proteins
Brain Natriuretic Peptide
Cyclic GMP
Fibroblasts
Fibronectins
Integrins
Collagen
Poly I
Lysine
Blocking Antibodies
Guanosine Monophosphate
Antibodies
Second Messenger Systems
Crosstalk
Matrix Metalloproteinases
Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

B-type natriuretic peptide and extracellular matrix protein interactions in human cardiac fibroblasts. / Huntley, Brenda K.; Ichiki, Tomoko; Sangaralingham, S Jeson; Chen, Horng Haur; Burnett, John C Jr.

In: Journal of Cellular Physiology, Vol. 225, No. 1, 10.2010, p. 251-255.

Research output: Contribution to journalArticle

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