scholarly journals Urban Particulate Matter Enhances ROS/IL-6/COX-II Production by Inhibiting MicroRNA-137 in Synovial Fibroblast of Rheumatoid Arthritis

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1378
Author(s):  
Ming-Horng Tsai ◽  
Miao-Ching Chi ◽  
Jen-Fu Hsu ◽  
I-Ta Lee ◽  
Ko-Ming Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Particulate Matter ◽  
Signaling Pathways ◽  
Synovial Fibroblast ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
In Vivo Studies ◽  
Ros Generation ◽  
Inflammatory Pathways ◽  
Mapk Signaling Pathways

Background: Rheumatoid arthritis (RA) has been associated with air pollution, possibly due to the augmentation of inflammatory effects. In this study, we aimed to determine the roles of inflammatory pathways and microRNA involved in the pathogenesis of RA fibroblast-like synoviocytes (FLS) inflammation induced by particulate matter. Methods: The inflammatory mediators, messenger RNAs, microRNAs and their interrelationships were investigated using western blotting, QPCR, ELISA and immunohistochemistry. Results: Particulate matter (PMs) induced an increase in the expression of interleukin-6 (IL-6) and cyclooxygenase-II (COX-II) in RA-FLS and microRNA-137 was found definitely to mediate the inflammatory pathways. PMs-induced generation of reactive oxygen species (ROS) in RA-FLS was attenuated by pretreatment with antioxidants. Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38 and JNK, followed by downregulation of microRNA-137. In vivo studies, the joints of rats exposed to PMs revealed synovial fibroblast inflammation under pathologic examination and the expressions of IL-6 and COX-II were obviously increased. PMs exposure results in activated ROS-mediated mitogen-activated protein kinase (MAPK) signaling pathways and cause increased IL-6 and COX-II through downregulation of hsa-miRNA-137, which lead to inflammation and RA exacerbation. Conclusions: microRNA-137 plays an important role in PMs-induced RA acute exacerbation through MAPK signaling pathways and IL-6/COX-II activation. Targeting these mechanisms can potentially be used to develop new therapeutic strategies and prevention of RA inflammation in the future.

scholarly journals Understanding MAPK Signaling Pathways in Apoptosis

2020 ◽  
Vol 21 (7) ◽  
pp. 2346 ◽  
Author(s):  
Jicheng Yue ◽  
José M. López
Keyword(s):  
Signaling Pathways ◽  
Positive Feedback ◽  
Cell Model ◽  
Mapk Signaling ◽  
Feedback Loops ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Mechanisms ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

MAPK (mitogen-activated protein kinase) signaling pathways regulate a variety of biological processes through multiple cellular mechanisms. In most of these processes, such as apoptosis, MAPKs have a dual role since they can act as activators or inhibitors, depending on the cell type and the stimulus. In this review, we present the main pro- and anti-apoptotic mechanisms regulated by MAPKs, as well as the crosstalk observed between some MAPKs. We also describe the basic signaling properties of MAPKs (ultrasensitivity, hysteresis, digital response), and the presence of different positive feedback loops in apoptosis. We provide a simple guide to predict MAPKs’ behavior, based on the intensity and duration of the stimulus. Finally, we consider the role of MAPKs in osmostress-induced apoptosis by using Xenopus oocytes as a cell model. As we will see, apoptosis is plagued with multiple positive feedback loops. We hope this review will help to understand how MAPK signaling pathways engage irreversible cellular decisions.

Electromyostimulation with blood flow restriction enhances activation of mTOR and MAPK signaling pathways in rat gastrocnemius muscles

2019 ◽  
Vol 44 (6) ◽  
pp. 637-644
Author(s):  
Toshiharu Natsume ◽  
Toshinori Yoshihara ◽  
Hisashi Naito
Keyword(s):  
Blood Flow ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Gastrocnemius Muscle ◽  
Lactate Concentration ◽  
Mapk Signaling ◽  
Blood Flow Restriction ◽  
Mitogen Activated Protein Kinase ◽  
Flow Restriction ◽  
Mapk Signaling Pathways

Neuromuscular electrical stimulation (NMES) combined with blood flow restriction (BFR) induces muscle hypertrophy. However, cellular mechanisms underlying the muscle hypertrophy induced by NMES combined with BFR remain unclear. We tested the hypothesis that NMES combined with BFR would enhance the mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways. Age-matched male Wistar rats (6 months old, n = 7 per group) were assigned randomly to control, BFR alone (BFR), NMES alone (NMES), and NMES combined with BFR (NMES/BFR) groups. NMES induced 25 isometric contractions lasting 8 s with 4-s resting periods between contractions in the gastrocnemius muscle. Four sets in total were performed, with 1-min intervals between sets. A latex cuff was placed on the proximal portion of the hind limb and BFR at 200 mm Hg was conducted in 4 sets (each set 5 min) with 1-min rest intervals between sets. Venous blood was collected from the lateral tail vein to determine pH, H+ concentration, and lactate concentration before and immediately after the treatments. Expression levels of proteins related to muscle hypertrophy were determined by Western blot analysis. The application of NMES/BFR promoted muscle fatigue more than NMES alone. NMES/BFR induced greater changes in accumulation of metabolites and increase in gastrocnemius muscle weight. The phosphorylation of mTOR and MAPK signaling-related proteins was also enhanced following NMES/BFR, compared with other conditions. Thus, NMES enhanced the activation of mTOR and MAPK signaling pathways when combined with BFR.

MAPK signaling pathways are needed for survival of H9c2 cardiac myoblasts under extracellular alkalosis

2008 ◽  
Vol 295 (3) ◽  
pp. H1319-H1329 ◽  
Author(s):  
Konstantina Stathopoulou ◽  
Isidoros Beis ◽  
Catherine Gaitanaki
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Cardiac Myocyte ◽  
Consensus Sequence ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Selective Inhibitors ◽  
Cardiac Myoblasts ◽  
Mapk Signaling Pathways

pH is one of the most important physiological parameters, with its changes affecting the function of vital organs like the heart. However, the effects of alkalosis on the regulation of cardiac myocyte function have not been extensively investigated. Therefore, we decided to study whether the mitogen-activated protein kinase (MAPK) signaling pathways [c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs), and p38 MAPK] are activated by alkalosis induced with Tris-Tyrode buffer at two pH values, 8.5 and 9.5, in H9c2 rat cardiac myoblasts. These buffers also induced intracellular alkalinization comparable to that induced by 1 mM NH4Cl. The three MAPKs examined presented differential phosphorylation patterns that depended on the severity and the duration of the stimulus. Inhibition of Na+/H+ exchanger (NHE)1 by its inhibitor HOE-642 prevented alkalinization and partially attenuated the alkalosis (pH 8.5)-induced activation of these kinases. The same stimulus also promoted c-Jun phosphorylation and enhanced the binding at oligonucleotides bearing the activator protein-1 (AP-1) consensus sequence, all in a JNK-dependent manner. Additionally, mitogen- and stress-activated kinase 1 (MSK1) was transiently phosphorylated by alkalosis (pH 8.5), and this was abolished by the selective inhibitors of either p38 MAPK or ERK pathways. JNKs also mediated Bcl-2 phosphorylation in response to incubation with the alkaline medium (pH 8.5), while selective inhibitors of the three MAPKs diminished cell viability under these conditions. All these data suggest that alkalosis activates MAPKs in H9c2 cells and these kinases, in turn, modify proteins that regulate gene transcription and cell survival.

scholarly journals Weaning Induced Hepatic Oxidative Stress, Apoptosis, and Aminotransferases through MAPK Signaling Pathways in Piglets

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Luo ◽  
Wei Zhu ◽  
Qi Guo ◽  
Wenli Luo ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Redox Status ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Hepatic Oxidative Stress ◽  
Mitogen Activated Protein ◽  
D 20 ◽  
Mapk Signaling Pathways

This study investigated the effects of weaning on the hepatic redox status, apoptosis, function, and the mitogen-activated protein kinase (MAPK) signaling pathways during the first week after weaning in piglets. A total of 12 litters of piglets were weaned at d 21 and divided into the weaning group (WG) and the control group (CG). Six piglets from each group were slaughtered at d 0 (d 20, referred to weaning), d 1, d 4, and d 7 after weaning. Results showed that weaning significantly increased the concentrations of hepatic free radicals H2O2and NO, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), while significantly decreasing the inhibitory hydroxyl ability (IHA) and glutathione peroxidase (GSH-Px), and altered the level of superoxide dismutase (SOD). The apoptosis results showed that weaning increased the concentrations of caspase-3, caspase-8, caspase-9 and the ratio of Bax/Bcl-2. In addition, aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT) in liver homogenates increased after weaning. The phosphorylated JNK and ERK1/2 increased, while the activated p38 initially decreased and then increased. Our results suggested that weaning increased the hepatic oxidative stress and aminotransferases and initiated apoptosis, which may be related to the activated MAPK pathways in postweaning piglets.

scholarly journals miR-143-3p Inhibits the Differentiation of Osteoclast Induced by Synovial Fibroblast and Monocyte Coculture in Adjuvant-Induced Arthritic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Baoping Jiang ◽  
Chengchen Yuan ◽  
Jing Han ◽  
Meiyu Shen ◽  
Xueping Zhou ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Early Stage ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Mapk Signaling ◽  
Primary Objective ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Inhibitors ◽  
Novel Strategy ◽  
Mapk Signaling Pathways

Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR-143-3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen-activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR-143-3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR-143-3p inhibited osteoclast differentiation and decreased the levels of M-CSF and RANKL during osteoclast differentiation. miR-143-3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR-143-3p expression in osteoclast differentiation. Taken together, our results suggested that miR-143-3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.

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