scholarly journals Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis

2020 ◽  
Author(s):  
Renyi Zhou ◽  
Yue Ma ◽  
Shui Qiu ◽  
Zunlei Gong ◽  
Xiaoshu Zhou
Keyword(s):  
Cell Proliferation ◽  
High Glucose ◽  
High Glucose Condition ◽  
Glucose Condition

scholarly journals Knockdown of FOXO6 inhibits cell proliferation and ECM accumulation in glomerular mesangial cells cultured under high glucose condition

RSC Advances ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 1741-1746 ◽  
Author(s):  
Yunqian Wang ◽  
Lei Xue ◽  
Huicong Li ◽  
Jun Shi ◽  
Baoping Chen
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Forkhead Box ◽  
High Glucose Condition ◽  
Glucose Condition ◽  
Cells Cultured

Forkhead box O 6 (FOXO6), a FOX transcription factor, has been found to be involved in diabetes mellitus and related complications.

scholarly journals The effects of high glucose condition on rat tenocytesin vitroand rat Achilles tendonin vivo

2018 ◽  
Vol 7 (5) ◽  
pp. 362-372 ◽  
Author(s):  
Y. Ueda ◽  
A. Inui ◽  
Y. Mifune ◽  
R. Sakata ◽  
T. Muto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Achilles Tendon ◽  
High Glucose ◽  
Type I Collagen ◽  
Diabetic Rats ◽  
Type I ◽  
High Glucose Condition ◽  
Glucose Condition

ObjectivesThe aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.MethodsUsing tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.ResultsIn tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased.ConclusionThis study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2

scholarly journals The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy

2018 ◽  
Vol 51 (3) ◽  
pp. 1410-1428 ◽  
Author(s):  
Yajuan Zhang ◽  
Yan Sun ◽  
Rui Peng ◽  
Handeng Liu ◽  
Weihao He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Noncoding Rna ◽  
Mapk Signaling ◽  
Luciferase Assay ◽  
Dependent Manner ◽  
High Glucose Condition ◽  
P38mapk Pathway ◽  
Glucose Condition

Background/Aims: Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. However, the initiating molecular events triggering DN are unknown. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in DN. Methods: The expression level of lncRNA 1500026H17Rik (150Rik for short) was measured by qRT-PCR (quantitative real-time PCR). Cell proliferation ability was detected by 5-Ethynyl-2’-deoxyuridine (EdU). The relationship between 150Rik and microRNA 451 (miR-451) was examined by luciferase assay and RNA immunoprecipitation (RIP) assay. Finally, the effect of 150Rik on cell proliferation through the miR-451/insulin-like growth factor 1 receptor (IGF1R)/mitogen-activated protein kinases (p38MAPK) pathway was detected by EdU, flow cytometry analysis, western blot. Results: We found that 150Rik, an evolutionarily conserved lncRNA, was significantly upregulated in renal tissue of db/db DN mice and in mesangial cells (MCs) cultured under a high glucose condition. Further, overexpression or knockdown of 150Rik was found to regulate cell proliferation in MCs. Moreover, 150Rik was found to interact with miR-451 in both a direct and argonaute-2 (Ago2)-dependent manner. Results also revealed that overexpression of 150Rik inhibited cell proliferation through the miR-451/IGF1R/p38MAPK pathway in MCs under the high glucose condition, while knockdown of 150Rik increased cell proliferation via the miR-451/IGF1R/p38MAPK pathway. Conclusion: Taken together, these results provide new insight into the association between 150Rik and the miR-451/IGF1R/p38MAPK signaling pathway during DN progression.

Effect of metformin and celecoxib on cytotoxicity and release of GDF-15 from human mesenchymal stem cells in high glucose condition

2017 ◽  
Vol 35 (7) ◽  
pp. 407-413 ◽  
Author(s):  
Elaheh Zafarvahedian ◽  
Azam Roohi ◽  
Mohammad Reza Sepand ◽  
Seyed Nasser Ostad ◽  
Mohammad Hossein Ghahremani
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Human Mesenchymal Stem Cells ◽  
High Glucose Condition ◽  
Glucose Condition

scholarly journals PPARβ/δ accelerates bone regeneration in diabetic mellitus by enhancing AMPK/mTOR pathway-mediated autophagy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miao Chen ◽  
Dian Jing ◽  
Rui Ye ◽  
Jianru Yi ◽  
Zhihe Zhao
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Bone Healing ◽  
High Glucose ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Regulatory Effect ◽  
Compound C ◽  
High Glucose Condition ◽  
Glucose Condition

Abstract Background Diabetic patients are more vulnerable to skeletal complications. Peroxisome proliferators-activated receptor (PPAR) β/δ has a positive regulatory effect on bone turnover under physiologic glucose concentration; however, the regulatory effect in diabetes mellitus has not been investigated yet. Herein, we explored the effects of PPARβ/δ agonist on the regeneration of diabetic bone defects and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) under a pathological high-glucose condition. Methods We detected the effect of PPARβ/δ agonist on osteogenic differentiation of rBMSCs in vitro and investigated the bone healing process in diabetic rats after PPARβ/δ agonist treatment in vivo. RNA sequencing was performed to detect the differentially expressed genes and enriched pathways. Western blot was performed to detect the autophagy-related protein level. Laser confocal microscope (LSCM) and transmission electron microscope (TEM) were used to observe the formation of autophagosomes. Results Our results demonstrated that the activation of PPARβ/δ can improve the osteogenic differentiation of rBMSCs in high-glucose condition and promote the bone regeneration of calvarial defects in diabetic rats, while the inhibition of PPARβ/δ alleviated the osteogenic differentiation of rBMSCs. Mechanistically, the activation of PPARβ/δ up-regulates AMPK phosphorylation, yielding mTOR suppression and resulting in enhanced autophagy activity, which further promotes the osteogenic differentiation of rBMSCs in high-glucose condition. The addition of AMPK inhibitor Compound C or autophagy inhibitor 3-MA inhibited the osteogenesis of rBMSCs in high-glucose condition, suggesting that PPARβ/δ agonist promotes osteogenic differentiation of rBMSCs through AMPK/mTOR-regulated autophagy. Conclusion In conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time.

ERM Complex, a Therapeutic Target for Vascular Leakage Induced by Diabetes

2021 ◽  
Vol 28 ◽  
Author(s):  
Olga Simó-Servat ◽  
Hugo Ramos ◽  
Patricia Bogdanov ◽  
Marta García-Ramírez ◽  
Jordi Huerta ◽  
...  
Keyword(s):  
High Glucose ◽  
Therapeutic Target ◽  
Vascular Leakage ◽  
Cell Permeability ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Erm Proteins ◽  
High Glucose Condition ◽  
Tnf Α ◽  
Glucose Condition

Background: Ezrin, radixin, and moesin (the ERM complex) interact directly with membrane proteins regulating their attachment to actin filaments. ERM protein activation modifies cytoskeleton organization and alters the endothelial barrier function, thus favoring vascular leakage. However, little is known regarding the role of ERM proteins in diabetic retinopathy (DR). Objective: This study aimed to examine whether overexpression of the ERM complex exists in db/db mice and its main regulating factors. Methods: 9 male db/db mice and 9 male db/+ aged 14 weeks were analyzed. ERM proteins were assessed by western blot and by immunohistochemistry. Vascular leakage was determined by the Evans blue method. To assess ERM regulation, HRECs were cultured in a medium containing 5.5 mM D-glucose (mimicking physiological conditions) and 25 mM D-glucose (mimicking hyperglycemia that occurs in diabetic patients). Moreover, treatment with TNF-α, IL-1β, or VEGF was added to a high glucose condition. The expression of ERM proteins was quantified by RT-PCR. Cell permeability was evaluated by measuring movements of FITC-dextran. Results: A significant increase of ERM in diabetic mice in comparison with non-diabetic mice was observed. A high glucose condition alone did not have any effect on ERM expression. However, TNF-α and IL-1β induced a significant increase in ERM proteins. Conclusion: The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.

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