SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling

Voelkl, Jakob; Luong, Trang T. D.; Tuffaha, Rashad; Musculus, Katharina; Auer, Tilman; Lian, Xiaoming; Daniel, Christoph; Zickler, Daniel; Boehme, Beate; Sacherer, Michael; Metzler, Bernhard; Kuhl, Dietmar; Gollasch, Maik; Amann, Kerstin; Müller, Dominik N.; Pieske, Burkert; Läng, Florian; Alesutan, Ioana

doi:10.1172/jci96477

Cited by 133 publications

(152 citation statements)

References 54 publications

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“…In liver tissue, excessive phosphate intake in rats is associated with increased AA concentrations (24). The osteogenic/chondrogenic transdifferentiated VSMCs are characterized by increased expression and activity of osteogenic and chondrogenic transcription factors as well as of osteogenic enzymes, such as tissue nonspecific ALPL, leading to active mineralization of the vascular tissue (22,(25)(26)(27). We show here that AACOCF3 treatment attenuates vascular osteogenic/chondrogenic transdifferentiation and calcification in vitro and in the cholecalciferol-overload mouse model in vivo.…”

Section: Discussionmentioning

confidence: 63%

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment

Schanstra¹,

Luong²,

Makridakis³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 63%

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment

Schanstra¹,

Luong²,

Makridakis³

et al. 2019

JCI Insight

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“…80,81 Moreover, MR inhibition reduces the expression of osteogenic transcription factors and mRNA levels of PIT1 and TNF-alpha. 84 The inhibition of MR signalling in VSMCs may therefore limit vascular calcification in CKD and cardiovascular diseases in CKD patients. 27,82 Aldosterone synthase expression is augmented in human aortic smooth muscle cells under conditions that favour vascular calcification, including klotho deficiency or excessive phosphate concentrations, likely enhancing aldosterone/MR participation in vascular calcification.…”

Section: Vascular Calcification In Vsmcs Is Mediated By the Mr In Cmentioning

confidence: 99%

“…The overexpression of a constitutively active form of SGK1 increases the expression of osteogenic proteins in VSMCs and promotes calcification. 84 The inhibition of MR signalling in VSMCs may therefore limit vascular calcification in CKD and cardiovascular diseases in CKD patients.…”

Section: Vascular Calcification In Vsmcs Is Mediated By the Mr In Cmentioning

confidence: 99%

Vascular and inflammatory mineralocorticoid receptors in kidney disease

Barrera‐Chimal

Jaisser

2019

Acta Physiologica

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Mineralocorticoid receptor (MR) activation in the kidney can occur outside the aldosterone-sensitive distal nephron in sites including the endothelium, smooth muscle and inflammatory cells. MR activation in these cells has deleterious effects on kidney structure and function by promoting oxidative injury, endothelial dysfunction and stiffness, vascular remodelling and calcification, decreased relaxation and activation of T cells and pro-inflammatory macrophages. Here, we review the data showing the cellular consequences of MR activation in endothelial, smooth muscle and inflammatory cells and how this affects the kidney in pathological situations. The evidence demonstrating a benefit of pharmacological or genetic MR inhibition in various models of kidney disease is also discussed.

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“…SGK1 leads to IkBa phosphorylation and NF-kB activation, which results in osteo-/chondrogenic transdifferentiation of VSMCs. Further study needs to be done in the future (49)(50)(51).…”

Section: Aacrjournalsorgmentioning

confidence: 99%

Serum- and Glucocorticoid-inducible Kinase 1 is Essential for Osteoclastogenesis and Promotes Breast Cancer Bone Metastasis

Zheng

Song

et al. 2020

Molecular Cancer Therapeutics

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◥Bone metastasis is a severe complication associated with various carcinomas. It causes debilitating pain and pathologic fractures and dramatically impairs patients' quality of life. Drugs aimed at osteoclast formation significantly reduce the incidence of skeletal complications and are currently the standard treatment for patients with bone metastases. Here, we reported that serum-and glucocorticoid-inducible kinase 1 (SGK1) plays a pivotal role in the formation and function of osteoclasts by regulating the Ca 2þ release-activated Ca 2þ channel Orai1. We showed that SGK1 inhibition represses osteoclastogenesis in vitro and prevents bone loss in vivo. Furthermore, we validated the effect of SGK1 on bone metastasis by using an intracardiac injection model in mice. Inhibition of SGK1 resulted in a significant reduction in bone metastasis. Subsequently, the Oncomine and the OncoLnc database were employed to verify the differential expression and the association with clinical outcome of SGK1 gene in patients with breast cancer. Our data mechanistically demonstrated the regulation of the SGK1 in the process of osteoclastogenesis and revealed SGK1 as a valuable target for curing bone metastasis diseases. Materials and Methods ReagentsGSK650394 and BTP2 was purchased from Sigma-Aldrich. Soluble recombinant human M-CSF and mouse RANKL were obtained from PeproTech.

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SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling

Cited by 133 publications

References 54 publications

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment

Vascular and inflammatory mineralocorticoid receptors in kidney disease

Serum- and Glucocorticoid-inducible Kinase 1 is Essential for Osteoclastogenesis and Promotes Breast Cancer Bone Metastasis

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