Expression and tissue localization of β-catenin, α-actinin and chondroitin sulfate proteoglycan 6 is modulated during rat and human left ventricular hypertrophy

Ridinger, Heidrun; Rutenberg, Christiane; Lutz, Diana M.; Buneß, Andreas; Petersen, Iver; Amann, Kerstin; Maercker, Christian

doi:10.1016/j.yexmp.2008.11.004

Cited by 7 publications

(5 citation statements)

References 43 publications

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“…One of these factors, Mkl1, itself regulates expression of cytoskeletal genes during megakaryopoiesis. Three of the factors, α-actinin, Hic-5, and Mkl1, have been implicated in cardiomyocyte hypertrophy (Kuwahara et al, 2010; Ridinger et al, 2009; Yund et al, 2009). Two of the factors, α-actinin and filamin A, function in actin cross-linkage, leading to F-actin stabilization (Mukhina et al, 2007; Nakamura et al, 2011), and our data suggest that α-actinin may regulate filamin A levels in megakaryocytes (Figure 6A).…”

Section: Discussionmentioning

confidence: 99%

Calpain 2 Activation of P-TEFb Drives Megakaryocyte Morphogenesis and Is Disrupted by Leukemogenic GATA1 Mutation

et al. 2013

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SUMMARY Megakaryocyte morphogenesis employs a “hypertrophy-like” developmental program, dependent on P-TEFb kinase activation and cytoskeletal remodeling. P-TEFb activation classically occurs by a feedback regulated process of signal-induced, reversible release of active Cdk9-cyclin T modules from large inactive 7SK snRNP complexes. Here we have identified an alternative pathway of irreversible P-TEFb activation in megakaryopoiesis, mediated by dissolution of the 7SK snRNP complex. In this pathway calpain 2 cleavage of the core 7SK snRNP component MePCE promoted P-TEFb release and consequent upregulation of a cohort of cytoskeleton remodeling factors, including α-actinin-1. In a subset of human megakaryocytic leukemias, the transcription factor GATA1 undergoes truncating mutation (GATA1s). Here we linked the GATA1s mutation to defects in megakaryocytic upregulation of calpain 2 and of P-TEFb-dependent cytoskeletal remodeling factors. Restoring calpain 2 expression in GATA1s-mutant megakaryocytes rescued normal development, implicating this morphogenetic pathway as a target in human leukemogenesis.

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Section: Discussionmentioning

confidence: 99%

Calpain 2 Activation of P-TEFb Drives Megakaryocyte Morphogenesis and Is Disrupted by Leukemogenic GATA1 Mutation

et al. 2013

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“…Although the actions of Klf7 and Sec62 in the heart are currently unknown, Klf7 has been reported as a susceptibility gene in type 2 diabetes (Kanazawa et al, 2005), and the overexpression of Klf7 in human adipocytes reportedly decreases adiponectin and leptin levels and increases IL-6 ( Kawamura et al, 2006). Moreover, a previous study demonstrated that the mRNA expression of Smc3 was increased in the rat model and patients with left ventricular hypertrophy (Ridinger et al, 2009). Finally, tissue inhibitor of metalloproteinase (TIMP)-3, an endogenous inhibitor of matrix metalloproteinases, may be involved in heart failure (Li et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Comparative effects of statins on murine cardiac gene expression profiles in normal mice

Ando

Ushijima

Fujimura

2013

European Journal of Pharmacology

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“…The capacity of SPARC to influence TGF-β1 signal transduction and myofibroblast differentiation will be discussed further below. In human heart disease, SPARC expression was found to be elevated in tissue sections from ventricles of individuals with left ventricular hypertrophy in one study [23]. More extensive characterization of SPARC in human heart disease will be an important and primary focus of future studies.…”

Section: Sparcmentioning

confidence: 99%

Cardiac extracellular matrix remodeling: Fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC)

McCurdy

Baicu

Heymans

et al. 2010

Journal of Molecular and Cellular Cardiology

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The cardiac interstitium is a unique and adaptable extracellular matrix (ECM) that provides a milieu in which myocytes, fibroblasts, and endothelial cells communicate and function. The composition of the ECM in the heart includes structural proteins such as fibrillar collagens and matricellular proteins that modulate cell:ECM interaction. Secreted Protein Acidic and Rich in Cysteine (SPARC), a collagen-binding matricellular protein, serves a key role in collagen assembly into the ECM. Recent results demonstrated increased cardiac rupture, dysfunction and mortality in SPARC-null mice in response to myocardial infarction that was associated with a decreased capacity to generate organized, mature collagen fibers. In response to pressure overload induced-hypertrophy, the decrease in insoluble collagen incorporation in the left ventricle of SPARC-null hearts was coincident with diminished ventricular stiffness in comparison to WT mice with pressure overload. This review will focus on the role of SPARC in the regulation of interstitial collagen during cardiac remodeling following myocardial infarction and pressure overload with a discussion of potential cellular mechanisms that control SPARC-dependent collagen assembly in the heart. Keywords BM-40; osteonectin; SPARC; extracellular matrix; remodeling; review Cardiac InterstitiumThe cardiac interstitium is composed primarily of collagen type I with lesser amounts of collagens type III and type V contributing to the majority of cardiac connective tissue [1]. The collagenous ECM of the heart undergoes relatively high rates of turnover in comparison to collagen in the ECM of other collagen-rich tissues such as dermis and tendon [2]. For example in adult rabbits, the collagen fractional synthesis rate is 8.94% in the heart and 0.86% in the skin [3]. In addition, cardiac fibrillar collagen is more insoluble than collagen in other tissues, due to increases in myocardial cross-linking of the interstitial collagen network [4]. Collagen

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Expression and tissue localization of β-catenin, α-actinin and chondroitin sulfate proteoglycan 6 is modulated during rat and human left ventricular hypertrophy

Cited by 7 publications

References 43 publications

Calpain 2 Activation of P-TEFb Drives Megakaryocyte Morphogenesis and Is Disrupted by Leukemogenic GATA1 Mutation

Calpain 2 Activation of P-TEFb Drives Megakaryocyte Morphogenesis and Is Disrupted by Leukemogenic GATA1 Mutation

Comparative effects of statins on murine cardiac gene expression profiles in normal mice

Cardiac extracellular matrix remodeling: Fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC)

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