CD226 reduces endothelial cell glucose uptake under hyperglycemic conditions with inflammation in type 2 diabetes mellitus

Zhang, Yuan; Tian, Li; Chen, Yu; Dong, Zilong; Zhang, Jinxue; Sun, Yizheng; Jin, Boquan; Gao, Feng; Guo, Shuzhong; Zhuang, Ran

doi:10.18632/oncotarget.7505

Cited by 14 publications

(15 citation statements)

References 29 publications

(27 reference statements)

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“…The data obtained demonstrated that the exposure of HUVECs to HG for 24 h led to injury and inflammation, as characterized by an increase in apoptotic cells, expression levels of caspase-3 (a death effector domain), oxidative stress (demonstrated by increased ROS production), decreased activation of SOd, increased expression of Nox4 (an important component of the NADPH oxidase family), increased expression level of eNOS, decreased cell viability and dissipation of MMP, and the upregulation of secretion of inflammatory cytokines (IL-1β, ll-6, IL-12 and TNF-α). These results are consistent with those of previous studies (5,(6)(7)(8)(9)(29)(30)(31) and demonstrated that the damage in HG-induced HUVEc injury and inflammation was extensive. However, the associated mechanism remains to be fully elucidated.…”

Section: Discussionsupporting

confidence: 93%

“…Ang- (1)(2)(3)(4)(5)(6)(7) and AG490 inhibit the HG-induced dissipation of MMP in HUVECs. It was shown that the exposure of HUVEcs to 40 mM glucose for 24 h elicited mitochondrial damage, as manifested by the dissipation of MMP ( Fig.…”

Section: Ang-(1-7) and Ag490 Suppress Hg-induced Apoptosis Inmentioning

confidence: 95%

“…Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway cardiovascular homeostasis is considered an important factor in the pathogenesis of diabetes-associated vascular complications (4,5). Studies have revealed that hyperglycemia induces numerous pathological changes in vascular endothelial cell injury, including oxidative stress (6), inflammation (7), increased endothelial cell apoptosis (6,8) and mitochondrial membrane permeabilization (9). However, the associated molecular mechanism by which hyperglycemia results in vascular endothelial cell injury in dM remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway

Chen

Zhang

et al. 2018

Int J Mol Med

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Angiotensin (Ang)‑1‑7, which is catalyzed by angiotensin‑converting enzyme 2 (ACE2) from angiotensin‑II (Ang‑II), exerts multiple biological and pharmacological effects, including cardioprotective effects and endothelial protection. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway has been demonstrated to be involved in diabetes‑associated cardiovascular complications. The present study hypothesized that Ang‑(1‑7) protects against high glucose (HG)‑induced endothelial cell injury and inflammation by inhibiting the JAK2/STAT3 pathway in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 40 mmol/l glucose (HG) for 24 h to establish a model of HG‑induced endothelial cell injury and inflammation. Protein expression levels of p‑JAK2, t‑JAK2, p‑STAT3, t‑STAT3, NOX‑4, eNOS and cleaved caspase‑3 were tested by western blotting. CCK‑8 assay was performed to assess cell viability of HUVECs. Apoptotic cell death was analyzed by Hoechst 33258 staining. Mitochondrial membrane potential (MMP) was obtained using JC‑1. Superoxide dismutase (SOD) activity was tested by SOD assay kit. Interleukin (IL)‑1β, IL‑10, IL‑12 and TNF‑α levels in culture media were tested by ELISA. The findings demonstrated that exposure of HUVECs to HG for 24 h induced injury and inflammation. This injury and inflammation were significantly ameliorated by pre‑treatment of cells with either Ang‑(1‑7) or AG490, an inhibitor of the JAK2/STAT3 pathway, prior to exposure of the cells to HG. Exposure of the cells to HG also increased the phosphorylation of JAK2/STAT3 (p‑JAK2 and p‑STAT3). Increased activation of the JAK2/STAT3 pathway was attenuated by pre‑treatment with Ang‑(1‑7). To the best of our knowledge, the findings from the present study provided the first evidence that Ang‑(1‑7) protects against HG‑induced injury and inflammation by inhibiting activation of the JAK2/STAT3 pathway in HUVECs.

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Section: Discussionsupporting

confidence: 93%

Section: Ang-(1-7) and Ag490 Suppress Hg-induced Apoptosis Inmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway

Chen

Zhang

et al. 2018

Int J Mol Med

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“…There are two types of DM; Type I DM in which the pancreatic beta cells do not produce insulin and Type II DM in which insulin is produced insufficient levels or it is not fully utilized by cells. Both types of DM are accompanied by major chronic complications, including microvascular complications such as neuropathy, nephropathy, and retinopathy, as well as undefined body weight loss [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress

et al. 2020

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Background: Diabetes mellitus is a global epidemic leads to multiple serious health complications, including nephropathy. Diabetic nephropathy is a serious kidney-related complication of type 1 or 2 diabetes that is prevalent in almost 40% of the people with diabetes. We examined whether folic acid and melatonin can reduce progression of nephropathy in rats of type 1 diabetes mellitus by controlling the level of oxidative stress, glucose, lipids, and cytokines. Methods: Forty-two male albino rats were distributed into six groups, (n = 7 per group). Five of the groups were induced with diabetes by a single intraperitoneal injection of freshly prepared streptozotocin at a dose of 50 mg/kg body weight. After the induction of diabetes, the rats were treated with folic acid (100 mg/kg) and melatonin (10 mg/kg) separately and in combination daily for 6 weeks, whereas, the other diabetic group was treated with glibenclamide (5 mg/kg). One of the diabetic groups served as a positive control. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons. Results: The data indicated that diabetes significantly altered the body weight, lipids and kidney function. Diabetic rats exhibited a significant increase in plasma levels of urea, uric acid, creatinine, sodium, tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), cholesterol, triglycerides, and low-density lipoprotein (LDL). In contrast, plasma total protein, potassium, high-density lipoprotein (HDL) and interleukin-10 (IL-10) decreased significantly in diabetic rats compared to the control rats. Moreover, levels of renal malondialdehyde (MDA) and nitric oxide (NO) were significantly increased while the levels of renal glutathione(GSH), superoxide dismutase(SOD), and catalase (CAT) were significantly decreased in diabetic rats comparison to those in the control rats. Hence, diabetic rats treated with folic acid and melatonin alone as well as in combination showed improvements with respect to the indices in addition to a significant recovery observed via histopathology when compared to the diabetic group. Conclusions: These results revealed that treatment with folic acid in combination with melatonin in diabetic rats was more effective than treatment with either of folic acid or melatonin alone to alleviate the symptoms of diabetic nephropathy.

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“…Hyperglycemia is an important factor for the injury to vascular endothelial cells. Its mechanism is multifaceted, including oxidative stress [10] , inflammatory response [11] , apoptosis [12] , mitochondrial injury [13] , and so forth, eventually leading to the occurrence of various diabetic vascular complications. In this study, 40 mmol/L glucose was used to treat HUVECs for 24 h so as to establish the HG-induced endothelial cell injury model.…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine resists high-glucose-induced injury of human umbilical vein endothelial cells by inhibiting the leptin/leptin receptor

Wang¹,

Lian

Liao

et al. 2020

Preprint

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Background The present study aimed to investigate whether N-acetylcysteine (NAC) protects human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced injury by inhibiting leptin/leptin receptor (LEPR).Methods HUVECs were treated with 40 mmol/L glucose for 24 h to establish a model of HG-induced endothelial cell injury; The cell viability was examined by cell counter kit-8 (CCK-8) assay; The expression levels of leptin, LEPR, cleaved caspase-3 and endothelial nitric oxide synthase (eNOS) were detected by western blot. The intracellular levels of reactive oxygen species (ROS) were tested by DCFH-DA staining followed by photofluorography. Tumor necrosis factor-α (TNF-α) nuclear factorkappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) were detected by enzyme-linked immunosorbent assay (ELISA). The number of apoptotic cells was observed by photofluorograph with Hoechst 33258 nuclear staining. Mitochondrial membrane potential (MMP) was obtained using JC-1. ResultsThe expression of leptin and LEPR began to significantly increase after exposure to 40 mmol/L HG for 24 h. Pretreatment of HUVECs with 7 mmol/L NAC or 50 ng/mL leptin antagonists (LA) for 30min inhibited the increased expression of leptin and LEPR induced by HG in HUVECs.Furthermore, pretreatment with 7 mmol/L NAC or 50 ng/mL LA for 30 min also inhibited HG-induced injury, by increasing the cell viability and eNOS expression, and decreasing the inflammatory response and cleaved caspase-3 expression, the apoptotic cells and generation of intracellular ROS and a loss of MMP.Conclusions NAC protects the HUVECs against HG-induced injury by inhibiting leptin/LEPR.

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CD226 reduces endothelial cell glucose uptake under hyperglycemic conditions with inflammation in type 2 diabetes mellitus

Cited by 14 publications

References 29 publications

Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway

Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway

Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress

N-acetylcysteine resists high-glucose-induced injury of human umbilical vein endothelial cells by inhibiting the leptin/leptin receptor

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