Expression of Concern: bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell Migration.
Ontology highlight
ABSTRACT:
SUBMITTER: PLOS ONE Editors
PROVIDER: S-EPMC9980763 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Expression of Concern: bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell Migration.
PloS one 20230302 3
Similar Datasets
Project description:One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.
| S-EPMC4171528 | biostudies-literature
Project description:Neural Wiskott-Aldrich syndrome protein (N-WASP) is an important member of the WASP family involved in the actin cytoskeleton reorganization. Recent evidence suggests that N-WASP may play important roles in tumor progression and metastasis. However, the contribution of N-WASP to cervical cancer is still unknown. The present study focused on elucidating the role of N-WASP in the malignant behavior of cervical cancer cells. We found that N-WASP overexpressed in cervical cancer tissues compared with paired paracancerous tissues and normal tissues, and similar results were observed in several cervical cancer cell lines. Furthermore, we demonstrated that overexpression of N-WASP facilitated migration and invasion of cervical cancer cells, while downregulation of N-WASP resulted in decreased cell migration and invasion. In addition, the data showed that N-WASP might promote invasion and migration of cervical cancer cells via regulating the activity of p38 MAPKs pathway. Altogether, the study suggested that N-WASP might serve as an oncogene in cervical cancer, and provided novel insights into the mechanism that how N-WASP promoted invasion and migration of cervical cancer cells.
| S-EPMC5340677 | biostudies-literature
Project description:Both phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis, and metastasis of tumor cells. In the present report, we investigated the effects of licochalcone A (LA), a flavonoid extracted from licorice root, on the PI3K/AKT/mTOR and MAPK activation pathways in human gastric cancer BGC-823 cells. LA increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding and activation of caspase-3, and cleavage of poly-ADP-ribose polymerase (PARP). Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented LA-induced apoptosis. Interestingly, we also observed that LA caused the activation of ERK, JNK, and p38 MAPK in BGC-823 cells. The antitumour activity of LA-treated BGC-823 cells was significantly distinct in KM mice in vivo. All the findings from our study suggest that LA can interfere with MAPK signaling cascades, initiate ROS generation, induce oxidative stress and consequently cause BGC cell apoptosis.
| S-EPMC4434846 | biostudies-other
Project description:Ultraviolet A (UVA) radiation is a major contributor to the pathogenesis of skin photoaging, and the aim of this study was to investigate the effect of Acacetin on skin photoaging in UVA-irradiated mice and human dermal fibroblasts (HDF). Healthy dorsal depilated rats were irradiated with UVA 30 J/cm2 daily, every other day, for 1 month. Acacetin (40, 80 mg kg/day) was coated to the bare skin of the rats' backs 1 h before UVA irradiation. HDF were treated different concentrations of Acacetin (5, 10, 20 μg/ml) and then irradiated with UVA (20 J/cm2 ). Acacetin was found to be effective in ameliorating UVA-induced oxidative stress and cell death. Acacetin also prevented the UVA-induced decrease of SIRT3, reduced the activation of mitogen-activated protein kinases (MAPKs, p-38 and p-JNK) and blocked the down-regulated activation of oxidative stress in matrix metalloproteinases (MMPs). In addition, Acacetin increased the expressions of collagen-promoting proteins (TGF-β and Smad3). Finally, the SIRT3 inhibitor 3-TYP blocked all protective effects of Acacetin, indicating that the protective effect of Acacetin against UVA photoaging is SIRT3-dependent. Acacetin effectively mitigated photoaging by targeting the promotion of SIRT3, inhibiting the UVA-induced increases in MMPs and pro-inflammatory factors, and promoting TGF-β and Smad3.
| S-EPMC9357640 | biostudies-literature
Project description: Not available
| S-EPMC7112199 | biostudies-literature
Project description:Previously, we identified RAD21R450C from a peripheral sclerocornea pedigree. Injection of this rad21 variant mRNA into Xenopus laevis embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous rad21 variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in X. laevis embryos. In X. laevis embryos injected with rad21 mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21R450C variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development.
| S-EPMC7594026 | biostudies-literature
Project description:Aims/hypothesisThe pancreas and hypothalamus are critical for maintaining nutrient and energy homeostasis, and combined disorders in these organs account for the onset of the metabolic syndrome. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. The physiological role of ATF3 in the pancreas has been controversial, and its role in the hypothalamus remains unknown. To elucidate the roles of ATF3 in these organs, we generated pancreas- and hypothalamus-specific Atf3 knockout (PHT-Atf3-KO) mice in this study.MethodsWe crossed mice bearing floxed Atf3 alleles with Pdx1-cre mice, in which cre is specifically expressed in the pancreas and hypothalamus, and analysed metabolic variables, pancreatic morphology, food intake, energy expenditure and sympathetic activity in adipose tissue. We also used a hypothalamic cell line to investigate the molecular mechanism by which ATF3 regulates transcription of the gene encoding agouti-related protein (Agrp).ResultsAlthough PHT-Atf3-KO mice displayed better glucose tolerance, neither plasma glucagon nor insulin level was altered in these mice. However, these mice exhibited higher insulin sensitivity, which was accompanied by a leaner phenotype due to decreased food intake and increased energy expenditure. We also observed decreased hypothalamic Agrp expression in PHT-Atf3-KO mice. Importantly, an increase in ATF3 levels is induced by fasting or low glucose in the hypothalamus. We also showed that ATF3 interacts with forkhead box-containing protein, O subfamily 1 (FoxO1) on the Agrp promoter and activates Agrp transcription.Conclusions/interpretationOur results suggest that ATF3 plays an important role in the control of glucose and energy metabolism by regulating Agrp.
| S-EPMC3648686 | biostudies-literature
Project description:Sunitinib is a multi-targeted tyrosine kinase inhibitor with remarkable anticancer activity, while hepatotoxicity is a potentially fatal adverse effect of its administration. The aim of this study was to elucidate the mechanism of hepatotoxicity induced by Sunitinib and the protective effect of glycyrrhetinic acid (GA). Sunitinib significantly reduced the survival of human normal hepatocytes (L02 cells), induced the increase of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Chloroquine (CQ) and Z-VAD-FMK were applied to clarify the cell death patterns induced by Sunitinib. Sunitinib significantly induced L02 cells death by triggering apoptosis and autophagy acted as a self-defense mechanism to promote survival. Sunitinib exposure caused excessive ROS generation which activated mitogen-activated protein kinases (MAPKs) signaling. Mechanistically, SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor) respectively blocked apoptosis and autophagy induced by Sunitinib. And inhibition of ROS by NAC pretreatment ameliorated the effect of Sunitinib on MAPKs phosphorylation. GA alleviated Sunitinib-induced cell damage by inhibiting apoptosis and autophagy. These results suggested ROS/MAPKs signaling pathway was responsible for Sunitinib-induced hepatotoxicity and GA could be a preventive strategy to alleviate liver injury caused by Sunitinib.
| S-EPMC9643779 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a primary cause of disability and mortality. Ghrelin, a gastrointestinal hormone, has been found to have protective effects for the brain, but the molecular mechanism of these neuroprotective effects of ghrelin remains unclear. In this study, an electronic cortical contusion impactor was used to establish a rat TBI model and we investigated the effect of ghrelin on brain repair by neurological severity score and histological examination. An antibody array was employed to uncover the molecular mechanism of ghrelin's neuroprotective effects by determining the alterations of multiple proteins in the brain cortex. As a result, ghrelin attenuated brain injury and promoted brain functional recovery. After TBI, 13 proteins were up-regulated in the brain cortex, while basic fibroblast growth factor (bFGF) and fibroblast growth factor-binding protein (FGF-BP) were down-regulated after ghrelin treatment. It is known that bFGF can induce angiogenesis in the brain and accelerate wound healing, which can be further enhanced by FGF-BP. Based on the previous studies, it is hypothesized that the exogenous ghrelin curing TBI might cause the closure of bFGF and FGF-BP functions on wound healing, or ghrelin might exert the neuroprotective effects by competitively inhibiting bFGF/FGF-BP-induced neovascularization. Whether the combinational administration of ghrelin and bFGF/FGF-BP can enhance or weaken the therapeutic effect on TBI requires further research.
| S-EPMC6041414 | biostudies-literature
Project description:Jaceosidin (JAC) is a natural flavonoid with anti-oxidant and other pharmacological activities; however, its anti-cancer mechanism remains unclear. We investigated the mechanism of action of JAC in gastric cancer cells. Cytotoxicity and apoptosis assays showed that JAC effectively killed multiple gastric cancer cells and induced apoptosis in human gastric adenocarcinoma AGS cells via the mitochondrial pathway. Network pharmacological analysis suggested that its activity was linked to reactive oxygen species (ROS), AKT, and MAPK signaling pathways. Furthermore, JAC accumulated ROS to up-regulate p-JNK, p-p38, and IκB-α protein expressions and down-regulate the p-ERK, p-STAT3, and NF-κB protein expressions. Cell cycle assay results showed that JAC accumulated ROS to up-regulate p21 and p27 protein expressions and down-regulate p-AKT, CDK2, CDK4, CDK6, Cyclin D1, and Cyclin E protein expressions to induce G0/G1 phase arrest. Cell migration assay results showed JAC accumulated ROS to down-regulate Wnt-3a, p-GSK-3β, N-cadherin, and β-catenin protein expressions and up-regulate E-cadherin protein expression to inhibit migration. Furthermore, N-acetyl cysteine pre-treatment prevented the change of these protein expressions. In summary, JAC induced apoptosis and G0/G1 phase arrest and inhibited migration through ROS-mediated signaling pathways in AGS cells.
| S-EPMC10854459 | biostudies-literature