Serum and glucocorticoid‐inducible kinase 1 (SGK1) is necessary for vascular remodeling during angiogenesis

Catela, Catarina; Kratsios, Paschalis; Hede, Marianne Smedegaard; Läng, Florian; Rosenthal, Nadia

doi:10.1002/dvdy.22345

Cited by 39 publications

(40 citation statements)

References 62 publications

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“…In this study, we demonstrated that a high‐fat diet increased both SGK1 abundance and Ser‐422 phosphorylation in the vasculature of DIO mice. Previous studies from our laboratory and others demonstrate that enhanced expression or activation of SGK1 exacerbate cellular processes that lead to pathological vascular remodeling . Thus, our findings suggest that SGK1 is activated in the vasculature with the onset of obesity and may participate in cellular processes that lead to vascular dysfunction.…”

Section: Discussionsupporting

confidence: 65%

SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet‐induced obesity

Scott

Babayeva

Banerjee

et al. 2016

Obesity

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Objective Enhanced serum and glucocorticoid-inducible kinase 1 (SGK1) activity contributes to the pathogenesis of vascular disease. We evaluated SGK1 modulation in vascular smooth muscle cells by the adipokine, resistin and in aortic tissue in a murine model of diet-induced obesity (DIO). Methods Modulation of SGK1 by resistin was assessed in human aortic smooth muscle cells (HAoSMC) in vitro by quantitative RT-PCR and western blot analyses. To induce the lean or obese phenotype, mice were fed a 10 kcal% low-fat or 60 kcal% high-fat diet, respectively for eight weeks. Upon study completion, plasma resistin was assessed and aortic tissue was harvested to examine the effect of DIO on regulation of SGK1 in vivo. Results Resistin increased SGK1 mRNA, total protein abundance and its activation as determined by phosphorylation of its serine 422 residue (pSGK1) in HAoSMC. Resistin-mediated SGK1 phosphorylation was dependent upon phosphatidylinositol-3-kinase and Toll-like receptor 4. Furthermore, inhibition of SGK1 attenuated resistin-induced proliferation in HAoSMC. DIO led to upregulation of total SGK1 protein levels and pSGK1 in association with increased plasma resistin. Conclusions These data suggest that high levels of resistin observed during obesity may activate SGK1 in the vasculature and contribute to the development of obesity-related vascular disease.

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Section: Discussionsupporting

confidence: 65%

SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet‐induced obesity

Scott

Babayeva

Banerjee

et al. 2016

Obesity

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“…SGK1 is up-regulated by ischemia [53,54] and may participate in the stimulation of tumor vascularization [55]. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of Colonic Tumor Growth by the Selective SGK Inhibitor EMD638683

Towhid

Liu

Ackermann

et al. 2013

Cell Physiol Biochem

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Background: The serum and glucocorticoid inducible kinase SGK1, which was originally cloned from mammary tumor cells, is highly expressed in some but not all tumors. SGK1 confers survival to several tumor cells. Along those lines, the number of colonic tumors following chemical carcinogenesis was decreased in SGK1 knockout mice. Recently, a highly selective SGK inhibitor (EMD638683) has been developed. The present study explored whether EMD638683 affects survival of colon carcinoma cells in vitro and impacts on development of colonic tumors in vivo. Methods: Colon carcinoma (Caco-2) cells were exposed to EMD638683 with or without exposure to radiation (3 Gray) and cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, mitochondrial potential from JC-9 fluorescence, caspase 3 activity from CaspGlow Fluorescein staining, DNA degradation from propidium iodide staining as well as late apoptosis from annexin-V FITC and propidium iodide double staining. In vivo tumor growth was determined in wild type mice subjected to chemical carcinogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium in drinking water for 7 days). Results: EMD638683 treatment significantly augmented the radiation-induced decrease of forward scatter, increase of phosphatidylserine exposure, decrease of mitochondrial potential, increase of caspase 3 activity, increase of DNA fragmentation and increase of late apoptosis. The in vivo development of tumors following chemical carcinogenesis was significantly blunted by treatment with EMD638683. Conclusions: EMD638683 promotes radiation-induced suicidal death of colon tumor cells in vitro and decreases the number of colonic tumors following chemical carcinogenesis in vivo.

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“…Furthermore, our laboratory demonstrated for the first time that genetic disruption of SGK1, which is activated in the myocardium by mIGF-1 overexpression (in parallel with PDK1 and JNK1), reduces the expression of Notch signaling genes in mouse embryos, impairing heart structure and function (Catela et al, 2010).…”

Section: Migf-1 Enhances Sirt1 Expression In Cardiomyocytes Through Jmentioning

confidence: 99%

mIGF‐1/JNK1/SirT1 signaling confers protection against oxidative stress in the heart

et al. 2011

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SummaryOxidative stress contributes to the pathogenesis of aging-associated heart failure. Among various signaling pathways mediating oxidative stress, the NAD + -dependent protein deacetylase SirT1 has been implicated in the protection of heart muscle. Expression of a locally acting insulin-like growth factor-1 (IGF-1) propeptide (mIGF-1) helps the heart to recover from infarct and enhances SirT1 expression in cardiomyocytes (CM) in vitro, exerting protection from hypertrophic and oxidative stresses. To study the role of mIGF-1 ⁄ SirT1 signaling in vivo, we generated cardiac-specific mIGF-1 transgenic mice in which SirT1 was depleted from adult CM in a tamoxifen-inducible and conditional fashion. Analysis of these mice confirmed that mIGF-1-induced SirT1 activity is necessary to protect the heart from paraquat (PQ)-induced oxidative stress and lethality. In cultured CM, mIGF-1 increases SirT1 expression through a c-Jun NH(2)-terminal protein kinase 1 (JNK1)-dependent signaling mechanism. Thus, mIGF-1 protects the heart from oxidative stress via SirT1 ⁄ JNK1 activity, suggesting new avenues for cardiac therapy during aging and heart failure.

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Serum and glucocorticoid‐inducible kinase 1 (SGK1) is necessary for vascular remodeling during angiogenesis

Cited by 39 publications

References 62 publications

SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet‐induced obesity

SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet‐induced obesity

Inhibition of Colonic Tumor Growth by the Selective SGK Inhibitor EMD638683

mIGF‐1/JNK1/SirT1 signaling confers protection against oxidative stress in the heart

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