Kruppel-like Factors (KLFs) in muscle biology

Haldar, Saptarsi M.; Ibrahim, Omer H. M.; Jain, Mukesh K.

doi:10.1016/j.yjmcc.2007.04.005

Cited by 88 publications

(67 citation statements)

References 99 publications

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“…64 Recent studies revealed the important role of KLFs as regulators of cardiac biology. 65 The family of KLFs was found to control ␤-catenin-dependent transcription in several tissue compartments like the gut and the heart. Possibly, KLF proteins allow for tissue specific control of ␤-catenin transcription because KLF4 regulates transcription in the small intestine whereas we found another member of the same family, namely KLF15, to control ␤-catenin-dependent transcription in the heart.…”

Section: Nuclear Negative Interaction Partners Of ␤-Catenin Attenuatementioning

confidence: 99%

WNT Signaling in Adult Cardiac Hypertrophy and Remodeling

2010

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Abstract:On pathological stress, the heart reactivates several signaling pathways that traditionally were thought to be operational only in the developing heart. One of these pathways is the WNT signaling pathway. WNT controls heart development but is also modulated during adult heart remodeling. This review summarizes the currently available data regarding WNT signaling during left ventricular (LV) remodeling. Upstream, soluble frizzled-related proteins (sFRPs) block WNT-dependent activation of the canonical WNT pathway. By inhibition of WNT activation, these factors also reduce ␤-catenin-dependent transcription by altering the ratio of cytoplasmic/nuclear ␤-catenin. In experimental settings, sFRPs injected into the heart attenuated LV remodeling. sFRPs are secreted from autologous bone marrow-derived mononuclear cells. Disheveled is a signaling intermediate of both the canonical and noncanonical WNT pathway. Similarly to the effect of sFRP, depletion of a disheveled isoform attenuated LV remodeling. In contrast, disheveled activation led to progressive dilated cardiomyopathy. Inhibition of nuclear ␤-catenin signaling downstream of the canonical WNT pathway significantly reduced postinfarct mortality and functional decline of LV function following chronic left anterior descending coronary artery ligation. WNT signaling also affects mobilization and homing of bone marrowderived vasculogenic progenitor cells. Finally, heart-specific WNT/␤-catenin interaction partners have been identified that will possibly allow targeting this pathway in a tissue-specific manner. In summary, the WNT pathway plays a pivotal role in adult cardiac remodeling and may be suitable for therapeutic interventions. Currently, several molecular and cellular mechanisms whereby WNT inhibition attenuates LV remodeling are proposed. Reactivation of the developmental program to restore functional LV myocardium from resident precursor cells may significantly contribute to this process.

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Section: Nuclear Negative Interaction Partners Of ␤-Catenin Attenuatementioning

confidence: 99%

WNT Signaling in Adult Cardiac Hypertrophy and Remodeling

2010

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“…KLFs are known to play several roles in muscle cell development (46), and it has been shown that in cardiac myocytes, expression of KLF3 changes rapidly in response to stimuli leading either to hypertrophy or apoptosis (29). KLF3 has also recently been identified as a transcriptional regulator of skeletal muscle differentiation (28).…”

Section: Klf3 and Muscle Cell Biologymentioning

confidence: 99%

The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)

2011

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KLF3 is a member of the Krüppel‐like factor (KLF) family of transcription factors. These proteins are classified by the presence of three C‐terminal C2H2 zinc fingers that allow sequence‐specific binding to CACCC boxes and GC‐rich motifs found in the promoters, enhancers, and other control regions of target genes. KLFs have diverse biological roles, regulating proliferation, differentiation, and apoptosis in many tissues throughout development. KLF3 is a transcriptional repressor that binds the cofactor C‐terminal binding protein, which in turn recruits a large repressor complex to mediate transcriptional silencing. In addition to an understanding of the molecular mechanisms that allow KLF3 to regulate the expression of its target genes, the biological roles of this transcription factor are now being defined. In agreement with the widespread expression pattern of this transcription factor, it is becoming clear that KLF3 is an important regulator of several biological processes, including adipogenesis, erythropoiesis, and B cell development. © 2011 IUBMB IUBMB Life, 63(2): 86–93, 2011

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“…Members of the Krüppel-like factor (KLF) family of transcription factors are important regulators of development, cellular differentiation and growth, and the pathogenesis of various diseases, including cancer and cardiovascular disease (13). We previously used Klf5 +/-mice to show that KLF5 is required for cardiac hypertrophy and fibrosis in response to continuous infusion of angiotensin II (AII) (14,15).…”

Section: Introductionmentioning

confidence: 99%

Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload

et al. 2010

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Fibroblasts, which are the most numerous cell type in the heart, interact with cardiomyocytes in vitro and affect their function; however, they are considered to play a secondary role in cardiac hypertrophy and failure. Here we have shown that cardiac fibroblasts are essential for the protective and hypertrophic myocardial responses to pressure overload in vivo in mice. Haploinsufficiency of the transcription factor-encoding gene Krüppel-like factor 5 (Klf5) suppressed cardiac fibrosis and hypertrophy elicited by moderate-intensity pressure overload, whereas cardiomyocyte-specific Klf5 deletion did not alter the hypertrophic responses. By contrast, cardiac fibroblast-specific Klf5 deletion ameliorated cardiac hypertrophy and fibrosis, indicating that KLF5 in fibroblasts is important for the response to pressure overload and that cardiac fibroblasts are required for cardiomyocyte hypertrophy. High-intensity pressure overload caused severe heart failure and early death in mice with Klf5-null fibroblasts. KLF5 transactivated Igf1 in cardiac fibroblasts, and IGF-1 subsequently acted in a paracrine fashion to induce hypertrophic responses in cardiomyocytes. Igf1 induction was essential for cardioprotective responses, as administration of a peptide inhibitor of IGF-1 severely exacerbated heart failure induced by high-intensity pressure overload. Thus, cardiac fibroblasts play a pivotal role in the myocardial adaptive response to pressure overload, and this role is partly controlled by KLF5. Modulation of cardiac fibroblast function may provide a novel strategy for treating heart failure, with KLF5 serving as an attractive target.

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Kruppel-like Factors (KLFs) in muscle biology

Cited by 88 publications

References 99 publications

WNT Signaling in Adult Cardiac Hypertrophy and Remodeling

WNT Signaling in Adult Cardiac Hypertrophy and Remodeling

The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)

Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload

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