Record Details

Signaling Mechanisms Regulating Fibroblast Activation, Phenoconversion and Fibrosis in the Heart

NOPR - NISCAIR Online Periodicals Repository

View Archive Info
 
 
Field Value
 
Title Signaling Mechanisms Regulating Fibroblast Activation, Phenoconversion and Fibrosis in the Heart
 
Creator MacLean, Jessica
Pasumarthi, Kishore B S
 
Subject Cardiac fibrosis
Myofibroblast
Phenoconversion
Signaling changes
Gene expression
 
Description 476-482
Cardiac
fibroblasts (CFs) maintain the cardiac extracellular matrix (ECM) through
myocardial remodelling. The remodelling process can become dysregulated during
various forms of heart disease which
leads to an overall accumulation of ECM. This results in cardiac fibrosis which increases the risk of heart
failure in many patients. During heart disease, quiescent CFs undergo
phenoconversion to an activated cell type called cardiac myofibroblasts (CMFs).
Factors influencing phenoconversion include transforming growth factor β
(TGF-β) which via SMADs (small mothers against decapentaplegic) activates the
myofibroblast marker gene αSMA (α smooth muscle actin). Signaling molecules as
diverse as NAD(P)H oxidase 4 (Nox4) and Wnt have been found to interact with
TGF-β signalling via SMADs. Pathways, including FAK/TAK/JNK and PI3K/Akt/rac
have also been implicated in activating phenoconversion of fibroblasts. Another
major contributor is mechanical stress exerted on CFs by ECM changes, which
involves activation of ERK and subsequent αSMA expression. Other factors, such
as the mast cell protease tryptase and the seeding density also affect the
phenoconversion of fibroblast cultures in
vitro. Further, reversal of myofibroblast phenotype has been reported by a
negative regulator of TGF-β, Ski, as well as the hormone relaxin and the second
messenger cAMP. Targeting the signaling molecules involved in promoting
phenoconversion of CFs to CMFs presents a possible method of controlling
cardiac fibrosis. Here, we provide a brief review of signaling mechanisms
responsible for phenoconversion and identify critical targets for the treatment
of cardiac fibrosis.
 
Date 2015-02-11T04:22:26Z
2015-02-11T04:22:26Z
2014-12
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/30496
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.51(6) [December 2014]