Premium
BNP‐induced activation of cGMP in human cardiac fibroblasts: Interactions with fibronectin and natriuretic peptide receptors
Author(s) -
Huntley Brenda K.,
Sandberg Sharon M.,
Noser Josh A.,
Cataliotti Alessandro,
Redfield Margaret M.,
Matsuda Yuzuru,
Burnett John C.
Publication year - 2006
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.20793
Subject(s) - fibronectin , natriuretic peptide , npr1 , receptor , npr2 , peptide , integrin , extracellular matrix , microbiology and biotechnology , brain natriuretic peptide , antagonist , chemistry , signal transduction , medicine , endocrinology , biology , heart failure , biochemistry
Cardiac remodeling involves the accumulation of extracellular matrix (ECM) proteins including fibronectin (FN). FN contains RGD motifs that bind integrins at DDX sequences allowing signaling from the ECM to the nucleus. We noted that the natriuretic peptide receptor A (NPR‐A) sequence contains both RGD and DDX sequences. The goal of the current investigation was to determine potential interactions between FN and NPR‐A on BNP induction of cGMP in cultured human cardiac fibroblasts (CFs). Further, we sought to determine whether a Mayo designed NPR‐A specific RGD peptide could modify this interaction. Here we reconfirm the presence of all three natriuretic peptide receptors (NPR) in CFs. CFs plated on FN demonstrated a pronounced increase in cGMP production to BNP compared to non‐coated plates. This production was also enhanced by the NPR‐A specific RGD peptide, which further augmented FN associated cGMP production. Addition of HS‐142‐1, a NPR‐A/B antagonist, abrogated the responses of BNP to both FN and the NPR‐A specific RGD peptide. Finally, we defined a possible role for the NPR‐C through non‐cGMP mechanisms in mediating the anti‐proliferative actions of BNP in CFs where the NPR‐C antagonist cANF 4‐28 but not HS‐142‐1 blocked BNP‐mediated inhibition of proliferation of CFs. We conclude that NPR‐A interacts with components of the ECM such as FN to enhance BNP activation of cGMP and that a small NPR‐A specific RGD peptide augments this action of BNP with possible therapeutic implications. Lastly, the NPR‐C may also have a role in mediating anti‐proliferative actions of BNP in CFs. J. Cell. Physiol. 209: 943–949, 2006. © 2006 Wiley‐Liss, Inc.