Type VI collagen induces cardiac myofibroblast differentiation: implications for post-infarction remodeling
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Naugle J E; Olson E R; Zhang X J; Mase S E; Pilati C F; Doane K J; Meszaros J G
Faseb Journal
2005
2005-03
Journal Article
<a href="http://doi.org/10.1152/ajpheart.00321.2005" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00321.2005</a>
Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase
adrenomedullin; angiotensin-ii; cardiac fibroblast; cyclic AMP; extracellular-matrix; failure; fibrosis; gene-expression; growth-factor-beta; heart; lung fibroblasts; modulation; necrosis-factor-alpha; phenotypic; rat ventricular myocytes; Science & Technology - Other Topics; smooth muscle actin
Transformation of fibroblasts to myofibroblasts, characterized by expression of alpha-smooth muscle actin (alpha-SMA) and production of extracellular matrix (ECM) components, is a key event in connective tissue remodeling. Approaches to inhibit this transformation are needed in tissues, such as the heart, where excessive ECM production by cardiac fibroblasts (CFs) causes fibrosis, myocardial stiffening, and cardiac dysfunction. We tested whether adenylyl cyclase (AC) activation (increased cAMP levels) modulates the transformation of adult rat CF to myofibroblasts, as assessed by immunofluorescent microscopy, immunoblotting, and collagen synthesis. A 24-h incubation of CF with TGF-beta or angiotensin II increased alpha-SMA expression, which was inhibited by the AC agonist forskolin and a cAMP analog that activates protein kinase A. Treatment with forskolin blunted serum-, TGF-beta-, and angiotensin II-stimulated collagen synthesis. CFs engineered to overexpress type 6 AC had enhanced forskolin-promoted cAMP formation, greater inhibition by forskolin of TGF-beta-stimulated alpha-SMA expression, and a decrease in the EC50 of forskolin to reduce serum-stimulated collagen synthesis. The AC stimulatory agonist adrenomedullin inhibited collagen synthesis in CF that overexpressed AC6 but not in controls. Thus, AC stimulation blunts collagen synthesis and, in parallel, the transformation of adult rat CF to myofibroblasts. AC overexpression enhances these effects, "uncovering" an inhibition by adrenomedullin. These findings implicate cAMP as an inhibitor of ECM formation by means of blockade of the transformation of CF to myofibroblasts and suggest that increasing AC expression, thereby enhancing cAMP generation through stimulation of receptors expressed on CF, could provide a means to attenuate and prevent cardiac fibrosis and its sequelae.
Swaney J S; Roth D M; Olson E R; Naugle J E; Meszaros J G; Insel P A
Proceedings of the National Academy of Sciences of the United States of America
2005
2005-01
Journal Article
<a href="http://doi.org/10.1073/pnas.0408704102" target="_blank" rel="noreferrer noopener">10.1073/pnas.0408704102</a>
Growth and differentiation of cardiac fibroblasts and myoribroblasts: regulation by collagen types I, III and cyclic AMP
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Naugle J E; Olson E R; Zhang X J; Mase S; Doane K J; Meszaros J G
Faseb Journal
2004
2004-03
Journal Article
n/a
Angiotensin II-induced cardiac fibroblast proliferation and ERK 1/2 activation is mediated by PKC zeta
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Olson E R; Naugle J E; Meszaros J G
Faseb Journal
2006
2006-03
Journal Article
n/a
Direct effects of resveratrol on cardiac fibroblasts: inhibition of calcium signaling, MAPK activation, and cellular growth
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Olson E R; Zhang X J; Marsh L; Meszaros J G; Bomser J A
Faseb Journal
2003
2003-03
Journal Article
n/a
Effects of resveratrol on cardiac fibroblasts: inhibition of MAPK regulated proliferation and myofibroblast differentiation
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Olson E R; Naugle J E; Zhang X J; Bomser J A; Meszaros J G
Faseb Journal
2004
2004-03
Journal Article
n/a
Opposing roles of alpha- and beta-adrenergic receptors in cardiac fibroblast differentiation
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Olson E R; Naugle J E; Kiraly F; Zhang X J; Meszaros J G
Faseb Journal
2005
2005-03
Journal Article
n/a
Cardiac fibroblast migration during in vitro wound healing: The role of specific collagen substrates
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Shamhart P E; Naugle J E; Olson E R; Liruska M A; Doane K J; Meszaros J G
Faseb Journal
2007
2007-04
Journal Article
n/a