Simvastatin Increases ADAMTS13 Expression in Podocytes

Shen, Lei; Lu, Guoyuan; Dong, Ningzheng; Ma, Zhengliang; Ruan, Changgeng

doi:10.1016/j.thromres.2013.05.024

Cited by 17 publications

(15 citation statements)

References 33 publications

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“…In podocytes, IL-4 and IL-6 differentially regulate ADAMTS13 mRNA and protein, which is reversed by simvastatin, a widely used antiatherosclerotic agent (35). In glial cells (astrocytes and microglia), ADAMTS13 expression is significantly upregulated after spinal cord injury (31), suggesting a potential role for ADAMTS13 in the central nervous system.…”

Section: Biosynthesis and Secretion Of Adamts13mentioning

confidence: 99%

ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

2015

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Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.

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Section: Biosynthesis and Secretion Of Adamts13mentioning

confidence: 99%

ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

2015

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“…Given that ADAMTS‐13 was discovered less than 20 years ago , environmental or dietary modulators of ADAMTS‐13 activity have not been extensively investigated. In vitro studies suggest statins may raise ADAMTS‐13 expression , whereas calcium and sodium chloride may reduce it .…”

Section: Resultsmentioning

confidence: 99%

ADAMTS‐13 activity and ischemic heart disease: a Mendelian randomization study

Schooling

Luo

Johnson

2018

Journal of Thrombosis and Haemostasis

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“…In vitro experiments have shown that these cells exhibit enhanced migration and invasion capacities; i.e. their mobility is enhanced, while in vivo experiments have demonstrated changes in the dynamic system of the podocytic processes and podocytic process fusion (Mao et al, 2013;Shen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Amiloride, a urokinase-type plasminogen activator receptor (uTPA) inhibitor, reduces proteinurea in podocytes

Chi

Shi

2015

Genet. Mol. Res.

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ABSTRACT. This study examined the mechanism of action of amiloride, a urokinase-type plasminogen activator receptor inhibitor, in lowering proteinuria. Podocytes were resuscitated to allow for their proliferation and were observed for morphological changes. In the in vitro experiment, control, lipopolysaccharide, and lipopolysaccharide + amiloride groups were established. The expression of urokinasetype plasminogen activator receptor (uPAR) in podocytes was detected with a flow cytometer and cell motility was detected with the transwell migration assay. In the in vivo test, the urine protein volume of the model was detected at 24 h using Coomassie brilliant blue staining and the morphological changes of the podocytes were detected with immunofluorescence. The protein expression rate of uPAR in the lipopolysaccharide group was significantly higher than those in the control and lipopolysaccharide + amiloride groups (P < 0.05). The viability of cells in the lipopolysaccharide group was significantly 9519 Amiloride lowers proteinuria in podocytes by uTPA inhibition ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 9518-9529 (2015) higher than those in the control and lipopolysaccharide + amiloride groups (P < 0.05). Compared with the urine protein level in the control group at 24 h, the level in the lipopolysaccharide group increased significantly (P < 0.05), whereas compared with the urine protein level in the lipopolysaccharide group, the level in the lipopolysaccharide + amiloride group decreased (P < 0.05). uPAR expression was significantly downregulated, and the fusion of the podocyte-specific skelemin synaptopodin on the glomerulus podocytes was significantly decreased in the lipopolysaccharide + amiloride group. These results suggest that amiloride is able to reduce cell motility and thus lower proteinuria by inhibiting the expression of uPAR in podocytes.

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Simvastatin Increases ADAMTS13 Expression in Podocytes

Cited by 17 publications

References 33 publications

ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

ADAMTS‐13 activity and ischemic heart disease: a Mendelian randomization study

Amiloride, a urokinase-type plasminogen activator receptor (uTPA) inhibitor, reduces proteinurea in podocytes

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