Effect of phosphorylated hsp27 on proliferation of human endothelial and smooth muscle cells

Trott, Deborah A.; McManus, Ciara A.; Martin, J.L.; Brennan, Bryony; Dünn, Michael J.; Rose, Marlene L.

doi:10.1002/pmic.200800961

Cited by 31 publications

(16 citation statements)

References 28 publications

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“…In agreement with our in vitro findings, another study found that overexpression of a phospho-mimic of HSPB1 caused changes in the actin cytoskeleton and reduced cytoskeletal plasticity, thereby increasing the pulmonary endothelial barrier (36). Other studies have shown that HSPB1 strongly colocalizes with cortical actin and is involved in endothelial cell adhesion and motility (45). Recently, we reported that the EndMT might be an early crucial step during RIPF, contributing to vascular collagen deposition appearing before tissue fibrosis (40).…”

Section: Discussionsupporting

confidence: 80%

HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis

et al. 2016

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The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFb or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non-small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases. Cancer Res; 76(5); 1019-30. Ó2016 AACR.

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Section: Discussionsupporting

confidence: 80%

HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis

et al. 2016

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“…Thereby, the protein enrichment increased species diversity by revealing HSP27 isoforms with different molecular weights or isoelectric point features that could not be detected in native extracts and thus qualified as of low abundance. Previous studies have reported that HSP27 can be present in different proteolytic fragments [37] and phosphorylated forms [38][39][40][41] or oligomers [42]. Moreover, increased HSP27 proteolysis in atherosclerotic plaques has also been reported in a secretome study [37].…”

Section: The Specific Case Of Hsp27 Species Expressionmentioning

confidence: 84%

Carotid atherosclerotic plaques: Proteomics study after a low‐abundance protein enrichment step

et al. 2012

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Atherosclerosis is one of the most important causes of cardiovascular and cerebrovascular events. Although phenotypic differentiation between stable and unstable plaques is currently possible, proteomic analysis of the atherosclerotic plaque could offer a global view of the atherosclerosis pathology. With the objective to highlight the detection of low-abundance proteins, we reduced the dynamic range of proteins by combinatorial peptide ligand library treatment of human carotid artery atherosclerotic plaques. After enrichment step, abundance of major proteins was decreased, revealing different protein profiles as assessed by both SDS-polyacrylamide gel electrophoresis and two-dimensional electrophoresis comparative analyses. Identification of proteins that were contained in a spot allowed finding large differences between noncomplicated and complicated plaques from carotid atherosclerotic lesions. Novel low-abundance proteins were detected correlating very well with biological alterations related to atherosclerosis (heat shock protein 27 (HSP27) isoforms, aldehyde dehydrogenase, moesin, Protein kinase C delta-binding protein, and inter-α trypsin inhibitor family heavy chain-related protein (ITIH4)). At the same time, the differential expression of known proteins of interest such as hemoglobin β-chain and heat shock protein 27 between noncomplicated and hemorrhagic complicated plaques was maintained after enrichment step. The detection of different isoforms of a low-abundance protein such as heat shock protein 27 species was actually improved after enrichment of tissue protein extracts. All of these findings clearly support further investigations in view to confirm the role of these proteins as possible biomarkers.

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“…FAK is known to promote endothelial cell migration, 33 while hyperphosphorylation of Hsp27 might promote cell cycle arrest. 34 There was also a strong decrease of PLCg-1 potentially linked to a mitogenic signal. 35,36 For BDNF, an increase for Mek ½, expressed downstream the TrkB signaling pathway, was observed.…”

Section: Blais Et Almentioning

confidence: 98%

Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-EngineeredIn VitroModel

Blais

Lévesque

Bellenfant

et al. 2013

Tissue Engineering Part A

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Skin is a major source of secretion of the neurotrophic factors nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory innervation. Beside their neuronal contribution, we hypothesized that neurotrophic factors also modulate the cutaneous microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human endothelial cells. We demonstrated that these peptides are highly potent angiogenic factors using a human tissue-engineered angiogenesis model. A 40% to 80% increase in the number of capillary-like tubes was observed after the addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and 50 ng/mL of GDNF. This is the first characterization of the direct angiogenic effect of NT-3 and GDNF. This angiogenic effect was mediated directly through binding with the neurotrophic factor receptors tropomyosin-receptor kinase A (TrkA), TrkB, GFRa-1 and c-ret that were all expressed by human endothelial cells, while this effect was blocked by addition of the Trk inhibitor K252a. Thus, if NGF, BDNF, NT-3, and GDNF may only moderately regulate the microvascular network in normal skin, they might have the potential to greatly increase angiogenesis in pathological situations.

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Effect of phosphorylated hsp27 on proliferation of human endothelial and smooth muscle cells

Cited by 31 publications

References 28 publications

HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis

HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis

Carotid atherosclerotic plaques: Proteomics study after a low‐abundance protein enrichment step

Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-EngineeredIn VitroModel

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