Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts

Mičutková, Lucia; Diener, Thomas; Li, Chen; Rogowska-Wrzesińska, Adelina; Mueck, Christoph; Huetter, Eveline; Weinberger, Birgit; Grubeck‐Loebenstein, Beatrix; Roepstorff, Peter; Zeng, Rong; Jansen-Duerr, Pidder

doi:10.1016/j.mad.2011.07.005

Cited by 31 publications

(31 citation statements)

References 66 publications

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“…Osteoprotegerin could regulate bone resorption, modeling, and remodeling, which is mainly secreted by osteoblasts [41, 42]. Meanwhile, IGFBP-6 could control the differentiation of cells and prevent the apoptosis and aging of human fibroblasts [43, 44]. IL-8, a chemokine of the immune system, could recruit neutrophils, endothelial cells, and macrophages to sites of injured tissues [45, 46].…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure

et al. 2017

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BackgroundHuman menstrual blood-derived stem cells (MenSCs) are a novel source of MSCs that provide the advantage of being easy to collect and isolate. Exosomes contain some mRNAs and adhesion molecules that can potentially impact cellular and animal physiology. This study aimed to investigate the therapeutic potential of MenSC-derived exosomes (MenSC-Ex) on AML12 cells (in vitro) and D-GalN/LPS-induced FHF mice (in vivo).MethodsTransmission electron microscopy and Western blot were used to identify MenSC-Ex. Antibody array was used to examine cytokine levels on MenSC-Ex. MenSC-Ex were treated in D-GalN/LPS-induced AML12 in vitro. Cell proliferation and apoptosis were measured. MenSC-Ex were injected into the tail veins of mice 24 h before treatment with D-GalN/LPS. Blood and liver tissues served as physiological and biochemical indexes. The number of liver mononuclear cells (MNCs) and the amount of the active apoptotic protein caspase-3 were determined to elaborate the mechanism of hepatoprotective activity.ResultsHuman menstrual blood-derived stem cell-derived exosomes (MenSC-Ex) are bi-lipid membrane vesicles that have a round, ball-like shape with a diameter of approximately 30–100 nm. Cytokine arrays have shown that MenSC-Ex expressed cytokines, including ICAM-1, angiopoietin-2, Axl, angiogenin, IGFBP-6, osteoprotegerin, IL-6, and IL-8. MenSC-Ex markedly improved liver function, enhanced survival rates, and inhibited liver cell apoptosis at 6 h after transplantation. MenSC-Ex migrated to sites of injury and to AML12 cells (a mouse hepatocyte cell line), respectively. Moreover, MenSC-Ex reduced the number of liver mononuclear cells (MNCs) and the amount of the active apoptotic protein caspase-3 in injured livers.ConclusionsIn conclusion, our results provide preliminary evidence for the anti-apoptotic capacity of MenSC-Ex in FHF and suggest that MenSC-Ex may be an alternative therapeutic approach to treat FHF.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0453-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure

et al. 2017

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“…(54,94,95). By contrast, IGFBP6 expression is associated with delayed replicative senescence of HDF (96). Our previous study of gene expression profiles during replicative senescence also demonstrated that IGFBP4 and IGFBP6 were downregulated, whereas IGFBP2, IGFBP3, IGFBP5, and IGFBP7 were upregulated (25), supporting their different contributions to senescence and the aging progress.…”

Section: Expression Of Sasp Regulatory Factorsmentioning

confidence: 66%

Erratum to: From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

et al. 2016

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The BMB Reports would like to correct in the reference of BMB Rep. 48(10), 549-558 titled "From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes". The REFERENCE should be corrected as red highlighting in this pages. This Erratum's doi is https://doi.org/10.5483/ BMBRep.2016.49.11.122. Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

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“…Therefore, elevated levels of Scx in PAI-1 knockout hearts may contribute to cardiac fibrogenesis; ii) IGFBP6 (Insulin like growth factor binding protein 6), a 29 kDa modulator of IGF activity, induces cellular proliferation, suppresses apoptosis and delays cellular senescence. IGFBP6 may be involved in liver fibrogenesis [50], [51] indicating elevated IGFBP6 in PAI-1 knockout hearts may play a role in cardiac-selective fibrogenesis; iii) Klf6, a 31 kDa zinc finger transcription factor, regulates TGF-β gene expression and is associated with fibrosis in non-alcoholic fatty liver diseases. Klf6 is also involved in oxidative stress-induced stellate cell activation, inflammation and increased collagen synthesis [52]–[54].…”

Section: Discussionmentioning

confidence: 99%

Global Gene Expression Profiling in PAI-1 Knockout Murine Heart and Kidney: Molecular Basis of Cardiac-Selective Fibrosis

et al. 2013

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Fibrosis is defined as an abnormal matrix remodeling due to excessive synthesis and accumulation of extracellular matrix proteins in tissues during wound healing or in response to chemical, mechanical and immunological stresses. At present, there is no effective therapy for organ fibrosis. Previous studies demonstrated that aged plasminogen activator inhibitor-1(PAI-1) knockout mice develop spontaneously cardiac-selective fibrosis without affecting any other organs. We hypothesized that differential expressions of profibrotic and antifibrotic genes in PAI-1 knockout hearts and unaffected organs lead to cardiac selective fibrosis. In order to address this prediction, we have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney. Analysis of illumina-based microarray data revealed that several genes involved in different biological processes such as immune system processing, response to stress, cytokine signaling, cell proliferation, adhesion, migration, matrix organization and transcriptional regulation were affected in hearts and kidneys by the absence of PAI-1, a potent inhibitor of urokinase and tissue-type plasminogen activator. Importantly, the expressions of a number of genes, involved in profibrotic pathways including Ankrd1, Pi16, Egr1, Scx, Timp1, Timp2, Klf6, Loxl1 and Klotho, were deregulated in PAI-1 knockout hearts compared to wildtype hearts and PAI-1 knockout kidneys. While the levels of Ankrd1, Pi16 and Timp1 proteins were elevated during EndMT, the level of Timp4 protein was decreased. To our knowledge, this is the first comprehensive report on the influence of PAI-1 on global gene expression profiling in the heart and kidney and its implication in fibrogenesis and several other biological processes. The significance of these observations in the light of heart-specific profibrotic signaling and fibrogenesis are discussed.

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Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts

Abstract: Highlights► Proteomic analysis of senescent secretome reveals upregulation of IGFBP-6 in fibroblasts. ► IGFBP-6 knockdown induces premature senescence in young fibroblasts. ► IGFBP-6 lentiviral overexpression delays replicative senescence in fibroblasts.

Cited by 31 publications

References 66 publications

Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure

Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure

Erratum to: From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

Global Gene Expression Profiling in PAI-1 Knockout Murine Heart and Kidney: Molecular Basis of Cardiac-Selective Fibrosis

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