• Title/Summary/Keyword: MAPK signaling pathway

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Analysis of MAPK Signaling Pathway Genes in the Intestinal Mucosal Layer of Necrotic Eenteritis-Afflicted Two Inbred Chicken Lines

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Korean Journal of Poultry Science
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    • v.44 no.3
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    • pp.199-209
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    • 2017
  • Mitogen-activated protein kinase (MAPK) signaling pathways play a key role in innate immunity, inflammation, cell proliferation, cell differentiation, and cell death. The main objective of this study was to investigate the expression level of candidate MAPK pathway genes in the intestinal mucosal layer of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE). Using high-throughput RNA sequencing, we investigated 178 MAPK signaling pathway related genes that were significantly and differentially expressed between the intestinal mucosal layers of the NE-afflicted and control chickens. In total, 15 MAPK pathway genes were further measured by quantitative real-time PCR(qRT-PCR) and the results were consistent with the RNA-sequencing data. All 178 identified genes were annotated through Gene Ontology and mapped onto the KEGG chicken MAPK signaling pathway. Several key genes of the MAPK pathway, ERK1/2, JNK1-3, p38 MAPK, MAP2K1-4, $NF-{\kappa}B1/2$, c-Fos, AP-1, Jun-D, and Jun, were differentially expressed in the two chicken lines. Therefore, we believe that RNA sequencing and qRT-PCR analysis provide resourceful information for future studies on MAPK signaling of genetically disparate chicken lines in response to pathogens.

Human amnion-derived mesenchymal stem cells induced osteogenesis and angiogenesis in human adipose-derived stem cells via ERK1/2 MAPK signaling pathway

  • Wang, Yuli;Chen, Xichen;Yin, Ying;Li, Song
    • BMB Reports
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    • v.51 no.4
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    • pp.194-199
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    • 2018
  • Mesenchymal stem cells (MSCs) have shown great potential in treating bone deficiency. Human adipose-derived stem cells (HASCs) are multipotent progenitor cells with multi-lineage differentiation potential. Human amnion-derived mesenchymal stem cells (HAMSCs) are capable of promoting osteogenic differentiation of MSCs. In this study, we investigated the effect of HAMSCs on HASCs by a transwell co-culture system. HAMSCs promoted proliferation, osteogenic differentiation, angiogenic potential and adiponectin (APN) secretion of HASCs. Moreover, the positive effect of HAMSCs was significantly inhibited by U0126, a highly selective inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway. These observations suggested that HAMSCs induced bone regeneration in HASCs via ERK1/2 MAPK signaling pathway.

IL-23 Inhibits Trophoblast Proliferation, Migration, and EMT via Activating p38 MAPK Signaling Pathway to Promote Recurrent Spontaneous Abortion

  • He, Shan;Ning, Yan;Ma, Fei;Liu, Dayan;Jiang, Shaoyan;Deng, Shaojie
    • Journal of Microbiology and Biotechnology
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    • v.32 no.6
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    • pp.792-799
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    • 2022
  • As a vital problem in reproductive health, recurrent spontaneous abortion (RSA) affects about 1% of women. We performed this study with an aim to explore the molecular mechanism of interleukin-23 (IL-23) and find optimal or effective methods to improve RSA. First, ELISA was applied to evaluate the expressions of IL-23 and its receptor in HTR-8/SVneo cells after IL-23 treatment. CCK-8, TUNEL, wound healing and transwell assays were employed to assess the proliferation, apoptosis, migration and invasion of HTR-8/SVneo cells, respectively. Additionally, the expressions of apoptosis-, migration-, epithelial-mesenchymal transition- (EMT-) and p38 MAPK signaling pathway-related proteins were measured by western blotting. To further investigate the relationship between IL-23 and p38 MAPK signaling pathway, HTR-8/SVneo cells were treated for 1 h with p38 MAPK inhibitor SB239063, followed by a series of cellular experiments on proliferation, apoptosis, migration and invasion, as aforementioned. The results showed that IL-23 and its receptors were greatly elevated in IL-23-treated HTR-8/SVneo cells. Additionally, IL-23 demonstrated suppressive effects on the proliferation, apoptosis, migration, invasion and EMT of IL-23-treated HTR-8/SVneo cells. More importantly, the molecular mechanism of IL-23 was revealed in this study; that is to say, IL-23 inhibited the proliferation, apoptosis, migration, invasion and EMT of IL-23-treated HTR-8/SVneo cells via activating p38 MAPK signaling pathway. In conclusion, IL-23 inhibits trophoblast proliferation, migration, and EMT via activating p38 MAPK signaling pathway, suggesting that IL-23 might be a novel target for the improvement of RSA.

Nectandrin A Enhances the BMP-Induced Osteoblastic Differentiation and Mineralization by Activation of p38 MAPK-Smad Signaling Pathway

  • Kim, Do Yeon;Kim, Go Woon;Chung, Sung Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.5
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    • pp.447-453
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    • 2013
  • Osteoblastic activity of nectandrin A was examined in C2C12 cells. Nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization, manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and increased calcium contents. In C2C12 cells co-transfected with expression vector encoding Smad4 and Id1-Luc reporter, nectandrin A increased Id1 luciferase activity in a concentration-dependent manner, when compared to that in BMP-2 treated cells, indicating that Smad signaling pathway is associated with nectandrin A-enhanced osteoblastic differentiation in C2C12 cells. In addition, nectandrin A activated p38 mitogen-activated protein kinase (MAPK) in time- and concentration-dependent manners, and phosphorylated form of pSmad1/5/8 and alkaline phosphatase activity were both decreased when the cells were pretreated with SB203580, a p38 MAPK inhibitor, suggesting that p38 MAPK might be an upstream kinase for Smad signaling pathway. Taken together, nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization of C2C12 cells via activation of p38 MAPK-Smad signaling pathway, and it has a therapeutic potential for osteoporosis by promoting bone formation.

Effect of Insulin-like Growth Factor-1 on Bone Morphogenetic Protein-2 Expression in Hepatic Carcinoma SMMC7721 Cells through the p38 MAPK Signaling Pathway

  • Xu, Guan-Jun;Cai, Sheng;Wu, Jian-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1183-1186
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    • 2012
  • Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

Shikonin ameliorates salivary gland damage and inflammation in a mouse model of Sjögren's syndrome by modulating MAPK signaling pathway

  • Wenjing Guo;Xin Wang;Chao Sun;Jian Wang;Tao Wang
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.357-364
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    • 2023
  • Sjögren syndrome (SS) is a systemic inflammatory autoimmune disease that involves exocrine glands. Shikonin is extracted from comfrey, which is conventionally used as an anti-tumor, antibacterial, and antiviral drug in China. However, the application of Shikonin in SS remains unreported. This study aimed to verify the potential functions of Shikonin in SS progression. Firstly, non-obese diabetic mice were used as the SS mouse model, with C57BL/6 mice serving as the healthy control. It was demonstrated that the salivary gland damage and inflammation were aggravated in the SS mouse model. Shikonin improved salivary gland function decline and injury in the SS mouse model. Moreover, Shikonin reduced inflammatory cytokines and immune infiltration in the SS mouse model. Further experiments discovered that Shikonin attenuated the MAPK signaling pathway in the SS mouse model. Lastly, inhibition of the MAPK signaling pathway combined with Shikonin treatment further alleviated the symptoms of SS. In conclusion, Shikonin ameliorated salivary gland damage and inflammation in a mouse model of SS by modulating the MAPK signaling pathway. Our findings indicate that Shikonin may be a useful drug for SS treatment.

Simulation for Signaling Pathway of MAPK Hypotonic Shock (MAPK Hypotonic Shock의 Signaling Pathway에 대한 시뮬레이션)

  • Jo, Mi-Kyung;Seo, Jeong-Man;Park, Hyun-Seok
    • Journal of the Korea Society of Computer and Information
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    • v.14 no.5
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    • pp.175-182
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    • 2009
  • We extracted protein signal delivery path from protein interaction data, using location information and weight of protein. We obtained the protein interaction data by experimenting in two-hybrid system using Yeast. We simulated function's data of Hypotonic Shock comparing to signal delivery path provided in KEGG from the results. We measured process running period as well. In future, this research can be key to discover the origin of various genetic diseases and develop treatment.

Molecular characterization of a novel rice(Oryza sativa L.) MAP kinase, OsEDRl, its role in defense signaling pathway.

  • Kim, Jung-A;Jwa, Nam-Soo
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.82-83
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    • 2003
  • Plants have evolved differently from animals having mobile activities. Thus, plants should have developed unique defense mechanisms against biotic/abiotic stresses to which plants are differently exposed, according to seasons. Most organisms have an conserved signaling network using mitogen-activated protein kinase (MAPK) cascade(s). The phenomenon implied that they are functionally very important in all organisms. In fact, they constitute one of the major components of signaling pathways involved in regulating a wide range of cellular activities from growth and development to cell death. Recently, complete MAPK cascade was first characterized in Arabidopsis from the receptor kinase (FLS2) through fellowing MEKKI -MKK4/MKK5-MPK3/MPK6-WRKY22/MRKY29 pathway. Whereas, MAPK cascade signaling pathway in monocot plant including rice (0ryza sativa L.), the most important of all food crops and an established monocot plant research model, MAPKinase kinase kinases (MAPKKK) of rice are the first upstream component of the MAPK cascade, but MAPKKK has been first identified and characterized in our lab and designated as, OsEDRl based on its homology with the Arabidopsis EDRI. The Arabidopsis EDRl was regarded as a negative regulator of defense response and the role of rice OsEDRl was analyzed. Transcriptional regulation of OsEDRl was detected under various stresses and immunoblotting analysis is going on to detect the level of OsEDRl protein in the mutants showing unique phenotype. We also introduced the constitutively active and the dominant negative forms of the OsEDRl for characterizing biological function.

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Specific Binding and Catalytic Activation of the MAPK-MKP Complex

  • Kim, Myeongbin;Ryu, Seong Eon
    • Biodesign
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    • v.6 no.4
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    • pp.79-83
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    • 2018
  • Mitogen-activated protein kinases (MAPKs) are one of the most important enzymes in various cellular activities, and the MAPK signaling pathway is implicated in many disorders. MAPK phosphatases (MKPs) are regulators that contain a MAPK-binding domain (MBD) for MAPK recognition, and a catalytic domain (CD), for dephosphorylation and inactivation of MAPKs. Due to their crucial role in regulating the MAPK pathway, MKPs are regarded as a potential drug target in various diseases. Attempts have also been made to regulate the MAPK pathway by reducing the MKP activity. For drug development, it is important to understand the key features of MAPK-MKP complex formation. This review summarizes the studies on MAPK-MKP complexes, mainly focusing on their selective recognition and catalytic activation.

5-bromoprotocatechualdehyde suppresses growth of human lung cancer cells through modulation of ROS and the AKT/MAPK signaling pathway

  • Jusnseong Kim;Eun-A Kim;Nalae Kang;Seong-Yeong Heo;Soo-Jin Heo
    • Journal of Marine Bioscience and Biotechnology
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    • v.15 no.2
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    • pp.49-58
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    • 2023
  • Early-stage lung cancer is the deadliest form of the disease. In this study, we investigated the anticancer activity of 5-bromoprotocatechualdehyde (BPCA) extracted from the seaweed Polysiphonia morrowii Harvey (P. morrowii) in lung cancer H460 cells. We extracted P. morrowii powder thrice with 80% aqueous methanol and separated the extract using high-performance liquid chromatography. We then tested BPCA's effects on cell viability, apoptosis, reactive oxygen species (ROS) generation, and protein expression Our results showed that BPCA inhibited tumor cell growth and ROS production and induced apoptosis through mitogen-activated protein kinase (MAPK) and AKT signaling pathways in lung cancer cells. When BPCA was combined with hydrogen peroxide, ROS production and apoptosis increased even further due to the regulation of AKT signaling and JNK-MAPKs pathways. These findings suggest that BPCA induces lung-cancer-cell death through ROS-mediated phosphorylation in AKT/MAPK signaling. This could lead to the development of new and effective treatments for early-stage lung cancer.