Advertisement

Topics

High glucose up-regulates osteopontin expression by FoxO1 activation in macrophage.

08:00 EDT 1st May 2019 | BioPortfolio

Summary of "High glucose up-regulates osteopontin expression by FoxO1 activation in macrophage."

Hyperglycemia plays a major role in the development of diabetic macrovascular complications, including atherosclerosis and restenosis, which are responsible for the most of disability and mortality in diabetic patients. Osteopontin (OPN) is an important factor involved in atherogenesis, and hyperglycemia enhances the transcriptional activity of FoxO1 which is closely association with insulin resistance and diabetes. Here we showed that plasma OPN levels were significantly elevated in type 2 diabetic patients and positively correlated with glycated albumin (GA). The more atherosclerotic lesions were observed in the aorta of diabetic apoE-/- mice analyzed by Sudan IV staining. High glucose increased both the mRNA and protein expression levels of OPN and inhibited the phosphorylation of FoxO1 in RAW 264.7 cells. Overexpression of wild type or constitutively active mutant FoxO1 promoted the expression levels of OPN, while the dominant-negative mutant FoxO1 decreased slightly the expression of OPN. Conversely, knockdown of FoxO1 reduced the expression of OPN. Luciferase reporter assay revealed that high glucose and overexpression of FoxO1 enhanced the activities of the OPN promoter region nt -1918 ~ -713. Furthermore, the interactions between FoxO1 and the OPN promoter were confirmed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). Our results suggest that high glucose upregulates OPN expression via FoxO1 activation, which would play a critical role in the development of diabetic atherogenesis.

Affiliation

Journal Details

This article was published in the following journal.

Name: The Journal of endocrinology
ISSN: 1479-6805
Pages:

Links

DeepDyve research library

PubMed Articles [30915 Associated PubMed Articles listed on BioPortfolio]

Phosphorylation of forkhead protein FoxO1 at Ser253 regulates glucose homeostasis in mice.

The transcription factor forkhead boxO1 (FoxO1) is a key mediator in the insulin signaling pathway and controls multiple physiological functions, including hepatic glucose production (HGP) and pancrea...

Glucagon regulates hepatic mitochondrial function and biogenesis through Foxo1.

Glucagon promotes hepatic glucose production maintaining glucose homeostasis in the fasting state. Glucagon maintains at high level in both diabetic animals and human, contributing to hyperglycemia. M...

PAQR3 regulates phosphorylation of FoxO1 in insulin-resistant HepG2 cells via NF-κB signaling pathway.

Insulin resistance is a significant feature of type 2 diabetes mellitus and glucose and lipid metabolism disorders. Activation of NF-κB signaling pathway plays an important role in the formation of i...

FOXO1 regulates uterine epithelial integrity and progesterone receptor expression critical for embryo implantation.

Successful embryo implantation requires a receptive endometrium. Poor uterine receptivity can account for implantation failure in women who experience recurrent pregnancy loss or multiple rounds of un...

PAR2 promotes M1 macrophage polarization and inflammation via FOXO1 pathway.

Macrophages polarization plays essential but different roles in most diseases such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Our previous study revealed that protease-ac...

Clinical Trials [9314 Associated Clinical Trials listed on BioPortfolio]

A Study to Investigate the Safety and Efficacy of an Anti-IFN-gamma mAb in Children With Systemic Juvenile Idiopathic Arthritis (sJIA) Developing Macrophage Activation Syndrome/ Secondary Hemophagocytic Lymphohistiocytosis (MAS/sHLH)

Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of systemic Juvenile Idiopath...

Mesothelin and Osteopontin as Diagnostic Markers in Patients With Mesothelioma or Atypical Mesothelial Hyperplasia

RATIONALE: Studying levels of mesothelin and osteopontin in samples of blood from patients with mesothelioma or atypical mesothelial hyperplasia may help doctors identify biomarkers relate...

Low-dose IL-2 ( Interleukin-2) Treatment in Macrophage Activation Syndrome(MAS)

The investigators evaluate the effectiveness and safeness of low-dose Recombinant Human Interleukin-2 (rhIL-2) for MAS.

A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study

RAGE (the receptor for advanced glycation end-products) is a marker of alveolar type I cell injury and a pivotal mediator of acute inflammation and innate immunity. RAGE pathway is highly ...

Characterization of the Inflammatory Profile of Patients With Macrophage Activation Syndrome Secondary to Bacterial Sepsis

The pathophysiology of macrophage activation syndrome has been mainly studied in pediatric genetic primary forms. There is little data in secondary forms related to bacterial sepsis. Becau...

Medical and Biotech [MESH] Definitions

A forkhead box transcription factor that is a major target of INSULIN signaling and regulator of metabolic homeostasis in response to OXIDATIVE STRESS. It binds to the insulin RESPONSE ELEMENT (IRE) and the related Daf-16 family binding element (DBE). Its activity is suppressed by insulin and it also regulates OSTEOBLAST proliferation, controls bone mass, and skeletal regulation of GLUCOSE metabolism. It promotes GLUCONEOGENESIS in HEPATOCYTES and regulates gene expression in ADIPOSE TISSUE. It is also an important CELL DEATH regulator. Chromosomal aberrations involving the FOXO1 gene occur in RHABDOMYOSARCOMA.

The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.

A winged-helix transcription factor that regulates GENE expression in metabolic tissues. It plays a role in HOMEOSTASIS of GLUCOSE and controls expression of GLUT2 PROTEIN.

A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.

A basic leucine zipper transcription factor that regulates expression of MHC CLASS II GENES through its binding to a conserved X-box DNA sequence in the promoter region. It regulates the expression of genes involved in the UNFOLDED PROTEIN RESPONSE.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Diabetes
Diabetes is a lifelong condition that causes a person's blood sugar level to become too high. The two main types of diabetes are: type 1 diabetes type 2 diabetes In the UK, diabetes affects approximately 2.9 million people. There are a...


Searches Linking to this Article