Phosphorylation of signal transducer and activator of transcription 3 induced by hyperglycemia is different with that induced by lipopolysaccharide or erythropoietin via receptor‑coupled signaling in cardiac cells

Chiu, Yu‐Hsin; Ku, Po-Ming; Cheng, Yung-Ze; Li, Yingxiao; Niu, Ho‐Shan

doi:10.3892/mmr.2017.7973

Cited by 6 publications

(8 citation statements)

References 57 publications

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“…There is no doubt that ROS induced by high glucose are responsible for STAT3 activation, similar to previous views. 13,19,27 Expression of the Enho gene is promoted by STAT3 11 and we confirmed it in HepG2 cells by silencing STAT3 with a specific inhibitor (Stattic). Therefore, hyperglycemia produced ROS to activate STAT3 to induce higher expression of Enho gene in HepG2 cells.…”

Section: Discussionsupporting

confidence: 55%

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<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

Kuo¹,

Cheng²,

Li³

et al. 2020

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Background: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed. Materials and Methods: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasisassociated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting. Results: In diabetic rats, the serum concentrations of adropin were increased in the vehicletreated group and decreased in the insulin-or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs. Conclusion: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.

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Section: Discussionsupporting

confidence: 55%

“…An increase in STAT3 phosphorylation by oxidative stress has been previously shown. 27 ROS generation by diacylglycerol (DAG)/protein kinase C (PKC) and the NADPH oxidase pathway has been observed in diabetes. 28 ROS and/or oxidative stress induced by glucose fluctuations and/or hyperglycemia mediate diabetic complications.…”

Section: Discussionmentioning

confidence: 99%

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

Kuo¹,

Cheng²,

Li³

et al. 2020

DMSO

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“…In the present study, hyperglycemia accelerated PanIN progression, with increases in pSTAT3 and MYC levels. STAT3 is known to be an upstream regulator of MYC [20,21], and its association with hyperglycemia has been reported in the kidneys [22], lungs [23], and heart [24]. In renal mesangial cells, hyperglycemia was shown to enhance the activation of STAT3 [25].…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia enhances pancreatic cancer progression accompanied by elevations in phosphorylated STAT3 and MYC levels

et al. 2020

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Diabetes mellitus is a well-known risk factor for pancreatic cancer. We focused on hyperglycemia, a main feature of diabetes mellitus, and uncovered its effect on precancerous pancreatic intraepithelial neoplasia (PanIN) progression. In vivo induction of hyperglycemia with 100 mg/kg streptozotocin in Kras LSL G12D Pdx1Cre (KP) mice promoted the PanIN formation and progression. Preconditioning with a high-or low-glucose medium for 28 days showed that a high-glucose environment increased cell viability and sphere formation in PANC-1, a Kras-mutant human pancreatic ductal adenocarcinoma cell line, and mPKC1, a Krasmutant murine pancreatic cancer cell line. In contrast, no changes were observed in BxPC3, a Kras-wild-type human pancreatic cancer cell line. Orthotopic injection of mPKC1 into the pancreatic tails of BL6/J mice showed that cells maintained in high-glucose medium grew into larger tumors than did those maintained in low-glucose medium. Hyperglycemia strengthened the STAT3 phosphorylation, which was accompanied by elevated MYC expression in Kras-mutant cells. Immunohistochemistry showed stronger phosphorylated STAT3 (pSTAT3) and MYC staining in PanINs from diabetic KP mice than in those from euglycemic counterparts. STAT3 inhibition with 1 μM STAT3 inhibitor STATTIC in Krasmutant pancreatic cell lines blocked the cell viability-and sphere formation-enhancing effects of the hyperglycemic environment and reversed the elevated pSTAT3 and MYC expression. MYC knockdown did not affect cell viability but did reduce sphere formation. No decrease in pSTAT3 expression was observed upon siMYC treatment. In conclusion, hyperglycemia, on a Kras-mutant background, aggravates the PanIN progression, which is accompanied by elevated pSTAT3 and MYC expression.

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“…17 STAT3 is also required during the pre-implantation period and decidualization. 4,17-20 Hyperglycemia promotes a specific pattern of STAT3 activation, as demonstrated in cardiomyocytes, 21 as well as in glomerular and tubulointerstitium. 22…”

Section: Discussionmentioning

confidence: 99%

Increased expression of STAT3 and SOCS3 in placenta from hyperglycemic rats

et al. 2019

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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by interleukin (IL)-6 and IL-10 that generate nearly opposing responses. The suppressor of cytokine signaling 3 (SOCS3) is the negative regulator of STAT3 and plays an important role in the negative regulation of the inflammatory process. Evidence has shown the importance of STAT3 and SOCS3 during implantation and normal pregnancy. However, little is known about the relationship of both factors under hyperglycemic condition. The aim of this study was to evaluate the placenta regions exhibiting immunopositivity for STAT3 and SOCS3 in hyperglycemic rats, as well as correlate these proteins with IL-10 and IL-6 levels. It was observed increased expression of STAT3 at the labyrinth (approximately 47% of increase compared to control) and junctional zone (approximately 32% of increase compared to control) from hyperglycemic placentas. Similar results were observed to SOCS3 (approximately 71% -labyrinth- and 53% -junctional zone- of increase compared to control). The levels of IL-10 were augmented at hyperglycemic placentas (approximately 1.5 fold of increase) and they were positively correlated with the increase of STAT3 at the labyrinth and SOCS at junctional zone. Therefore, under hyperglycemic conditions, the relation between STAT3 and SOCS3 was changed, leading to unbalance of the cytokine profile.

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Phosphorylation of signal transducer and activator of transcription 3 induced by hyperglycemia is different with that induced by lipopolysaccharide or erythropoietin via receptor‑coupled signaling in cardiac cells

Cited by 6 publications

References 57 publications

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

Hyperglycemia enhances pancreatic cancer progression accompanied by elevations in phosphorylated STAT3 and MYC levels

Increased expression of STAT3 and SOCS3 in placenta from hyperglycemic rats

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