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Shumin Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury.
    Nature communications, 2015
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury

  • Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury
    Nature communications, 2014
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Interferon Regulatory Factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized 'IRF9-SIRT1 axis' in vasculoproliferative pathology modulation.

  • Interferon Regulatory Factor 3 protects against adverse neo-intima formation
    Cardiovascular Research, 2014
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Zuo-zhi Li, Pi-xiao Wang, Hongjing Guan, Xiao-fei Zhang, Ke Chen, Song Tian
    Abstract:

    Aims Vascular smooth muscle cell (VSMC) proliferation is central to the pathophysiology of neo-intima formation. Interferon Regulatory Factor 3 (IRF3) inhibits the growth of cancer cells and fibroblasts. However, the role of IRF3 in vascular neo-intima formation is unknown. We evaluated the protective role of IRF3 against neo-intima formation in mice and the underlying mechanisms. Methods and results IRF3 expression was down-regulated in VSMCs after carotid wire injury in vivo , and in SMCs after platelet-derived growth Factor (PDGF)-BB challenge in vitro . Global knockout of IRF3 (IRF3-KO) led to accelerated neo-intima formation and proliferation of VSMCs, whereas the opposite was seen in SMC-specific IRF3 transgenic mice. Mechanistically, we identified IRF3 as a novel regulator of peroxisome proliferator-activated receptor γ (PPARγ), a negative regulator of SMC proliferation after vascular injury. Binding of IRF3 to the AB domain of PPARγ in the nucleus of SMCs facilitated PPARγ transactivation, resulting in decreased proliferation cell nuclear antigen expression and suppressed proliferation. Overexpression of wild-type, but not truncated, IRF3 with a mutated IRF association domain (IAD) retained the ability to exert anti-proliferative effect. Conclusions IRF3 inhibits VSMC proliferation and neo-intima formation after vascular injury through PPARγ activation.

  • Interferon Regulatory Factor 9 protects against cardiac hypertrophy by targeting myocardin
    Hypertension, 2014
    Co-Authors: Dingsheng Jiang, Houzao Chen, Shumin Zhang, Ran Zhang, Yan Zhang, Xiaodong Zhang, Ke Chen, Hongliang Li
    Abstract:

    Pathological cardiac hypertrophy is a major risk Factor for heart failure. In this study, we identified Interferon Regulatory Factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac hypertrophy. The level of IRF9 expression was remarkably elevated in the hearts from animals with aortic banding–induced cardiac hypertrophy. IRF9-deficient mice exhibited pronounced cardiac hypertrophy after pressure overload, as demonstrated by increased cardiomyocyte size, extensive fibrosis, reduced cardiac function, and enhanced expression of hypertrophy markers, whereas transgenic mice with cardiac-specific overexpression of murine IRF9 exhibited a significant reduction in the hypertrophic response. Mechanistically, IRF9 competes with p300 for binding to the transcription activation domain of myocardin, a coactivator of serum response Factor (SRF). This interaction markedly suppresses the transcriptional activity of myocardin because IRF9 overexpression strongly inhibits the ability of myocardin to activate CArG box–dependent reporters. These results provide compelling evidence that IRF9 inhibits the development of cardiac hypertrophy by suppressing the transcriptional activity of myocardin in the heart.

  • Interferon Regulatory Factor 7 deficiency prevents diet-induced obesity and insulin resistance.
    American journal of physiology. Endocrinology and metabolism, 2013
    Co-Authors: Xin-an Wang, Dingsheng Jiang, Shumin Zhang, Ran Zhang, Shan Deng, Jinfeng Zhong, Li Yang, Wang Tao, Shufen Hong, Sen Guo
    Abstract:

    Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of Interferon Regulatory Factor 7 (IRF...

Dingsheng Jiang - One of the best experts on this subject based on the ideXlab platform.

  • Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury.
    Nature communications, 2015
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury

  • Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury
    Nature communications, 2014
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Interferon Regulatory Factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized 'IRF9-SIRT1 axis' in vasculoproliferative pathology modulation.

  • Interferon Regulatory Factor 3 protects against adverse neo-intima formation
    Cardiovascular Research, 2014
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Zuo-zhi Li, Pi-xiao Wang, Hongjing Guan, Xiao-fei Zhang, Ke Chen, Song Tian
    Abstract:

    Aims Vascular smooth muscle cell (VSMC) proliferation is central to the pathophysiology of neo-intima formation. Interferon Regulatory Factor 3 (IRF3) inhibits the growth of cancer cells and fibroblasts. However, the role of IRF3 in vascular neo-intima formation is unknown. We evaluated the protective role of IRF3 against neo-intima formation in mice and the underlying mechanisms. Methods and results IRF3 expression was down-regulated in VSMCs after carotid wire injury in vivo , and in SMCs after platelet-derived growth Factor (PDGF)-BB challenge in vitro . Global knockout of IRF3 (IRF3-KO) led to accelerated neo-intima formation and proliferation of VSMCs, whereas the opposite was seen in SMC-specific IRF3 transgenic mice. Mechanistically, we identified IRF3 as a novel regulator of peroxisome proliferator-activated receptor γ (PPARγ), a negative regulator of SMC proliferation after vascular injury. Binding of IRF3 to the AB domain of PPARγ in the nucleus of SMCs facilitated PPARγ transactivation, resulting in decreased proliferation cell nuclear antigen expression and suppressed proliferation. Overexpression of wild-type, but not truncated, IRF3 with a mutated IRF association domain (IAD) retained the ability to exert anti-proliferative effect. Conclusions IRF3 inhibits VSMC proliferation and neo-intima formation after vascular injury through PPARγ activation.

  • Interferon Regulatory Factor 9 protects against cardiac hypertrophy by targeting myocardin
    Hypertension, 2014
    Co-Authors: Dingsheng Jiang, Houzao Chen, Shumin Zhang, Ran Zhang, Yan Zhang, Xiaodong Zhang, Ke Chen, Hongliang Li
    Abstract:

    Pathological cardiac hypertrophy is a major risk Factor for heart failure. In this study, we identified Interferon Regulatory Factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac hypertrophy. The level of IRF9 expression was remarkably elevated in the hearts from animals with aortic banding–induced cardiac hypertrophy. IRF9-deficient mice exhibited pronounced cardiac hypertrophy after pressure overload, as demonstrated by increased cardiomyocyte size, extensive fibrosis, reduced cardiac function, and enhanced expression of hypertrophy markers, whereas transgenic mice with cardiac-specific overexpression of murine IRF9 exhibited a significant reduction in the hypertrophic response. Mechanistically, IRF9 competes with p300 for binding to the transcription activation domain of myocardin, a coactivator of serum response Factor (SRF). This interaction markedly suppresses the transcriptional activity of myocardin because IRF9 overexpression strongly inhibits the ability of myocardin to activate CArG box–dependent reporters. These results provide compelling evidence that IRF9 inhibits the development of cardiac hypertrophy by suppressing the transcriptional activity of myocardin in the heart.

  • Interferon Regulatory Factor 7 deficiency prevents diet-induced obesity and insulin resistance.
    American journal of physiology. Endocrinology and metabolism, 2013
    Co-Authors: Xin-an Wang, Dingsheng Jiang, Shumin Zhang, Ran Zhang, Shan Deng, Jinfeng Zhong, Li Yang, Wang Tao, Shufen Hong, Sen Guo
    Abstract:

    Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of Interferon Regulatory Factor 7 (IRF...

Yan Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury.
    Nature communications, 2015
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury

  • Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury
    Nature communications, 2014
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Interferon Regulatory Factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized 'IRF9-SIRT1 axis' in vasculoproliferative pathology modulation.

  • Interferon Regulatory Factor 9 protects against cardiac hypertrophy by targeting myocardin
    Hypertension, 2014
    Co-Authors: Dingsheng Jiang, Houzao Chen, Shumin Zhang, Ran Zhang, Yan Zhang, Xiaodong Zhang, Ke Chen, Hongliang Li
    Abstract:

    Pathological cardiac hypertrophy is a major risk Factor for heart failure. In this study, we identified Interferon Regulatory Factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac hypertrophy. The level of IRF9 expression was remarkably elevated in the hearts from animals with aortic banding–induced cardiac hypertrophy. IRF9-deficient mice exhibited pronounced cardiac hypertrophy after pressure overload, as demonstrated by increased cardiomyocyte size, extensive fibrosis, reduced cardiac function, and enhanced expression of hypertrophy markers, whereas transgenic mice with cardiac-specific overexpression of murine IRF9 exhibited a significant reduction in the hypertrophic response. Mechanistically, IRF9 competes with p300 for binding to the transcription activation domain of myocardin, a coactivator of serum response Factor (SRF). This interaction markedly suppresses the transcriptional activity of myocardin because IRF9 overexpression strongly inhibits the ability of myocardin to activate CArG box–dependent reporters. These results provide compelling evidence that IRF9 inhibits the development of cardiac hypertrophy by suppressing the transcriptional activity of myocardin in the heart.

Elizabeth A. Eklund - One of the best experts on this subject based on the ideXlab platform.

  • pu 1 Interferon Regulatory Factor irf 2 and the Interferon consensus sequence binding protein icsbp irf8 cooperate to activate nf1 transcription in differentiating myeloid cells
    Journal of Biological Chemistry, 2007
    Co-Authors: Weiqi Huang, Elizabeth Horvath, Elizabeth A. Eklund
    Abstract:

    Abstract Nf1 (neurofibromin 1) is a Ras-GAP protein that regulates cytokine-induced proliferation of myeloid cells. In previous studies, we found that the Interferon consensus sequence-binding protein (ICSBP; also referred to as Interferon Regulatory Factor 8) activates transcription of the gene encoding Nf1 (the NF1 gene) in differentiating myeloid cells. We also found that NF1 activation requires cytokine-stimulated phosphorylation of a conserved tyrosine residue in the Interferon Regulatory Factor (IRF) domain of ICSBP/IRF8. In this study, we found that ICSBP/IRF8 cooperates with PU.1 and Interferon Regulatory Factor 2 to activate a composite ets/IRF-cis element in the NF1 promoter. We found that PU.1 binds directly to the NF1-cis element, and DNA-bound PU.1 interacts with IRF2, recruiting IRF2 to the cis element. This interaction requires cytokine-induced phosphorylation of specific serine residues in the PU.1 PEST domain and of a conserved tyrosine residue in the IRF domain of IRF2. We found that ICSBP/IRF8 interaction with the NF1-cis element requires pre-binding of PU.1 and IRF2. The conserved IRF domain tyrosine in ICSBP/IRF8 is required for interaction with the DNA-bound PU.1-IRF2 heterodimer. NF1 deficiency in myeloid progenitor cells results in cytokine hypersensitivity and myeloproliferation. Therefore, these studies identify a target gene for the previously observed tumor-suppressor effect of PU.1. Additionally, these studies identify a tumor-suppressor function for the “oncogenic” transcription Factor, IRF2.

  • PU.1, Interferon Regulatory Factor (IRF) 2, and the Interferon Consensus Sequence-binding Protein (ICSBP/IRF8) Cooperate to Activate NF1 Transcription in Differentiating Myeloid Cells
    Journal of Biological Chemistry, 2007
    Co-Authors: Weiqi Huang, Elizabeth Horvath, Elizabeth A. Eklund
    Abstract:

    Abstract Nf1 (neurofibromin 1) is a Ras-GAP protein that regulates cytokine-induced proliferation of myeloid cells. In previous studies, we found that the Interferon consensus sequence-binding protein (ICSBP; also referred to as Interferon Regulatory Factor 8) activates transcription of the gene encoding Nf1 (the NF1 gene) in differentiating myeloid cells. We also found that NF1 activation requires cytokine-stimulated phosphorylation of a conserved tyrosine residue in the Interferon Regulatory Factor (IRF) domain of ICSBP/IRF8. In this study, we found that ICSBP/IRF8 cooperates with PU.1 and Interferon Regulatory Factor 2 to activate a composite ets/IRF-cis element in the NF1 promoter. We found that PU.1 binds directly to the NF1-cis element, and DNA-bound PU.1 interacts with IRF2, recruiting IRF2 to the cis element. This interaction requires cytokine-induced phosphorylation of specific serine residues in the PU.1 PEST domain and of a conserved tyrosine residue in the IRF domain of IRF2. We found that ICSBP/IRF8 interaction with the NF1-cis element requires pre-binding of PU.1 and IRF2. The conserved IRF domain tyrosine in ICSBP/IRF8 is required for interaction with the DNA-bound PU.1-IRF2 heterodimer. NF1 deficiency in myeloid progenitor cells results in cytokine hypersensitivity and myeloproliferation. Therefore, these studies identify a target gene for the previously observed tumor-suppressor effect of PU.1. Additionally, these studies identify a tumor-suppressor function for the “oncogenic” transcription Factor, IRF2.

Ran Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury.
    Nature communications, 2015
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Corrigendum: Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury

  • Interferon Regulatory Factor 9 is critical for neointima formation following vascular injury
    Nature communications, 2014
    Co-Authors: Shumin Zhang, Dingsheng Jiang, Houzao Chen, Ran Zhang, Song Tian, Li-hua Zhu, Peng Zhang, Lu Gao, Lang Wang, Yan Zhang
    Abstract:

    Interferon Regulatory Factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized 'IRF9-SIRT1 axis' in vasculoproliferative pathology modulation.

  • Interferon Regulatory Factor 9 protects against cardiac hypertrophy by targeting myocardin
    Hypertension, 2014
    Co-Authors: Dingsheng Jiang, Houzao Chen, Shumin Zhang, Ran Zhang, Yan Zhang, Xiaodong Zhang, Ke Chen, Hongliang Li
    Abstract:

    Pathological cardiac hypertrophy is a major risk Factor for heart failure. In this study, we identified Interferon Regulatory Factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac hypertrophy. The level of IRF9 expression was remarkably elevated in the hearts from animals with aortic banding–induced cardiac hypertrophy. IRF9-deficient mice exhibited pronounced cardiac hypertrophy after pressure overload, as demonstrated by increased cardiomyocyte size, extensive fibrosis, reduced cardiac function, and enhanced expression of hypertrophy markers, whereas transgenic mice with cardiac-specific overexpression of murine IRF9 exhibited a significant reduction in the hypertrophic response. Mechanistically, IRF9 competes with p300 for binding to the transcription activation domain of myocardin, a coactivator of serum response Factor (SRF). This interaction markedly suppresses the transcriptional activity of myocardin because IRF9 overexpression strongly inhibits the ability of myocardin to activate CArG box–dependent reporters. These results provide compelling evidence that IRF9 inhibits the development of cardiac hypertrophy by suppressing the transcriptional activity of myocardin in the heart.

  • Interferon Regulatory Factor 7 deficiency prevents diet-induced obesity and insulin resistance.
    American journal of physiology. Endocrinology and metabolism, 2013
    Co-Authors: Xin-an Wang, Dingsheng Jiang, Shumin Zhang, Ran Zhang, Shan Deng, Jinfeng Zhong, Li Yang, Wang Tao, Shufen Hong, Sen Guo
    Abstract:

    Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of Interferon Regulatory Factor 7 (IRF...