scholarly journals Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development

2020 ◽  
Vol 48 (20) ◽  
pp. 11452-11467
Author(s):  
Yenan Yang ◽  
Xiaoli Zhu ◽  
Xiang Jia ◽  
Wanwan Hou ◽  
Guoqiang Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Limb Development ◽  
Early Stage ◽  
Control Cell ◽  
Cell Lineage ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Embryonic Limb ◽  
Underlying Mechanisms

Abstract Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18. Accordingly, knockdown or antibody neutralization of Fgf9/18 inhibits Msx1-activated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Mechanistically, we determined that the phosphorylation of Msx1 at Ser136 is critical for enhancing Fgf9 and Fgf18 expression and cell proliferation, and cyclin-dependent kinase 1 (CDK1) is apparently responsible for Ser136 phosphorylation. Furthermore, mesenchymal deletion of Msx1/2 results in decreased Fgf9 and Fgf18 expression and Erk1/2 phosphorylation, which leads to serious defects in limb development in mice. Collectively, our findings established an important function of the Msx1-Fgf-MAPK signaling axis in promoting cell proliferation, thus providing a new mechanistic insight into limb development.

scholarly journals JCPyV-Induced MAPK Signaling Activates Transcription Factors during Infection

2019 ◽  
Vol 20 (19) ◽  
pp. 4779 ◽  
Author(s):  
Jeanne K. DuShane ◽  
Colleen L. Mayberry ◽  
Michael P. Wilczek ◽  
Sarah L. Nichols ◽  
Melissa S. Maginnis
Keyword(s):  
Transcription Factors ◽  
Mapk Signaling ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Downstream Signaling ◽  
Dual Specificity ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

JC polyomavirus (JCPyV), a ubiquitous human pathogen, is the etiological agent of the fatal neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Like most viruses, JCPyV infection requires the activation of host-cell signaling pathways in order to promote viral replication processes. Previous works have established the necessity of the extracellular signal-regulated kinase (ERK), the terminal core kinase of the mitogen-activated protein kinase (MAPK) cascade (MAPK-ERK) for facilitating transcription of the JCPyV genome. However, the underlying mechanisms by which the MAPK-ERK pathway becomes activated and induces viral transcription are poorly understood. Treatment of cells with siRNAs specific for Raf and MAP kinase kinase (MEK) targets proteins in the MAPK-ERK cascade, significantly reducing JCPyV infection. MEK, the dual-specificity kinase responsible for the phosphorylation of ERK, is phosphorylated at times congruent with early events in the virus infectious cycle. Moreover, a MAPK-specific signaling array revealed that transcription factors downstream of the MAPK cascade, including cMyc and SMAD4, are upregulated within infected cells. Confocal microscopy analysis demonstrated that cMyc and SMAD4 shuttle to the nucleus during infection, and nuclear localization is reduced when ERK is inhibited. These findings suggest that JCPyV induction of the MAPK-ERK pathway is mediated by Raf and MEK and leads to the activation of downstream transcription factors during infection. This study further defines the role of the MAPK cascade during JCPyV infection and the downstream signaling consequences, illuminating kinases as potential therapeutic targets for viral infection.

scholarly journals 15-deoxy-Δ12,14-prostaglandin J2Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Seung-Won Park ◽  
Chunghee Cho ◽  
Byung-Nam Cho ◽  
Youngchul Kim ◽  
Tae Won Goo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hepg2 Cells ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Activin A ◽  
Mitogen Activated Protein Kinase ◽  
Erk Phosphorylation ◽  
Mitogen Activated Protein ◽  
Regulatory Effects ◽  
Activin Receptors

15-Deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) and activin are implicated in the control of apoptosis, cell proliferation, and inflammation in cells. We examined both the mechanism by which 15d-PGJ2regulates the transcription of activin-induced activin receptors (ActR) and Smads in HepG2 cells and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in this regulation. Activin A (25 ng/mL) inhibited HepG2 cell proliferation, whereas 15d-PGJ2(2 μM and 5 μM) had no effect. Activin A and 15d-PGJ2showed different regulatory effects on ActR and Smad expression, NF-κB p65 activity and MEK/ERK phosphorylation, whereas they both decreased IL-6 production and increased IL-8 production. When co-stimulated with 15d-PGJ2and activin, 15d-PGJ2inhibited the activin-induced increases in ActR and Smad expression, and decreased activin-induced IL-6 production. However, it increased activin-induced IL-8 production. In addition, 15d-PGJ2inhibited activin-induced NF-κB p65 activity and activin-induced MEK/ERK phosphorylation. These results suggest that 15d-PGJ2suppresses activin-induced ActR and Smad expression, down-regulates IL-6 production, and up-regulates IL-8 production via suppression of NF-κB and MAPK signaling pathway in HepG2 cells. Regulation of ActR and Smad transcript expression and cytokine production involves NF-κB and the MAPK pathway via interaction with 15d-PGJ2/activin/Smad signaling.

scholarly journals Noncanonical auxin signaling regulates cell division pattern during lateral root development

2019 ◽  
Vol 116 (42) ◽  
pp. 21285-21290 ◽  
Author(s):  
Rongfeng Huang ◽  
Rui Zheng ◽  
Jun He ◽  
Zimin Zhou ◽  
Jiacheng Wang ◽  
...  
Keyword(s):  
Cell Division ◽  
Root Development ◽  
Lateral Root ◽  
Control Cell ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Auxin Signaling ◽  
Lateral Root Development ◽  
Division Pattern ◽  
Mitogen Activated Protein

In both plants and animals, multiple cellular processes must be orchestrated to ensure proper organogenesis. The cell division patterns control the shape of growing organs, yet how they are precisely determined and coordinated is poorly understood. In plants, the distribution of the phytohormone auxin is tightly linked to organogenesis, including lateral root (LR) development. Nevertheless, how auxin regulates cell division pattern during lateral root development remains elusive. Here, we report that auxin activates Mitogen-Activated Protein Kinase (MAPK) signaling via transmembrane kinases (TMKs) to control cell division pattern during lateral root development. Both TMK1/4 and MKK4/5-MPK3/6 pathways are required to properly orient cell divisions, which ultimately determine lateral root development in response to auxin. We show that TMKs directly and specifically interact with and phosphorylate MKK4/5, which is required for auxin to activate MKK4/5-MPK3/6 signaling. Our data suggest that TMK-mediated noncanonical auxin signaling is required to regulate cell division pattern and connect auxin signaling to MAPK signaling, which are both essential for plant development.

scholarly journals Linc02381 Exacerbates Rheumatoid Arthritis Through Adsorbing miR-590-5p and Activating the Mitogen-Activated Protein Kinase Signaling Pathway in Rheumatoid arthritis-fibroblast-like synoviocytes

2020 ◽  
Vol 29 ◽  
pp. 096368972093802
Author(s):  
Jing Wang ◽  
Qing Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Synovial Tissues ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. New evidence suggested that linc02381 suppressed colorectal cancer progression by regulating PI3 K signaling pathway, but the role of linc02381 in other diseases, such as RA, remains unclear. This study aimed to reveal the mechanism of linc02381 in RA progression. In vivo and in vitro, we found that linc02381 was upregulated in RA synovial tissues or RA fibroblast-like synoviocytes (RA-FLSs, P < 0.01), which were detected by quantitative real-time polymerase chain reaction. Cell Counting Kit-8, EDU, and Transwell assays revealed that linc02381 overexpression enhanced cell proliferation and invasion, and linc02381 knockdown inhibited cell proliferation and invasion in FLSs. Moreover, the results of bioinformatics analysis, luciferase reporter gene assay, and pull-down assay verified that linc02381 could directly bind with miR-590-5p. MiR-590-5p was downregulated in RA-FLSs, and overexpression of linc02381 suppressed expression of miR-590-5p that post-transcriptionally suppressed the expression of mitogen-activated protein kinase kinase 3 (MAP2K3), and overexpression of miR-590-5p reversed the effect of linc02381 overexpression on MAP2K3 expression. MiR-590-5p inhibitor reversed the inhibition effect of linc02381 knockdown on proliferation and invasion of FLSs, which enhanced expression of MAP2K3, and activation of p38 and AP-1 in the MAPK signaling pathway. In summary, linc02381 was upregulated in RA synovial tissues and RA-FLSs, and it exacerbated RA by adsorbing miR-590-5p to activate the MAPK signaling pathway.

scholarly journals Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 96 ◽  
Author(s):  
Tong Wang ◽  
Xiaoxia Jin ◽  
Yingjun Liao ◽  
Qi Sun ◽  
Chaohong Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Activator Protein 1 ◽  
Mitogen Activated Protein ◽  
Rat Astrocytes ◽  
Underlying Mechanisms ◽  
Matrix Metalloproteinases 9 ◽  
Pathological Consequence

Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE. In the present study, we analyzed the association of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) with MMP-9 overexpression in astrocytes treated with 2-CE. MMP-9, p65, c-Jun, and c-Fos were significantly upregulated by 2-CE treatment, which also enhanced phosphorylation of c-Jun, c-Fos and inhibitor of κBα (IκBα), and nuclear translocation of p65. Furthermore, inhibition of IκBα phosphorylation and AP-1 activity with the specific inhibitors could attenuate MMP-9 overexpression in the cells. On the other hand, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway suppressed the activation of both NF-κB and AP-1 in 2-CE-treated astrocytes. In conclusion, MMP-9 overexpression induced by 2-CE in astrocytes could be mediated at least in part through the p38 signaling pathway via activation of both NF-κB and AP-1. This study might provide novel clues for clarifying the mechanisms underlying 1,2-DCE associated cerebral edema.

scholarly journals P62dok, a Negative Regulator of Ras and Mitogen-Activated Protein Kinase (Mapk) Activity, Opposes Leukemogenesis by P210bcr-abl

2001 ◽  
Vol 194 (3) ◽  
pp. 275-284 ◽  
Author(s):  
Antonio Di Cristofano ◽  
Masaru Niki ◽  
Mingming Zhao ◽  
Fredrick G. Karnell ◽  
Bayard Clarkson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Protein Kinase ◽  
Tyrosine Kinases ◽  
Bone Marrow Cells ◽  
Mapk Signaling ◽  
Negative Regulator ◽  
Myelogenous Leukemia ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

p62dok has been identified as a substrate of many oncogenic tyrosine kinases such as the chronic myelogenous leukemia (CML) chimeric p210bcr-abl oncoprotein. It is also phosphorylated upon activation of many receptors and cytoplamic tyrosine kinases. However, the biological functions of p62dok in normal cell signaling as well as in p210bcr-abl leukemogenesis are as yet not fully understood. Here we show, in hemopoietic and nonhemopoietic cells derived from p62dok−/− mice, that the loss of p62dok results in increased cell proliferation upon growth factor treatment. Moreover, Ras and mitogen-activated protein kinase (MAPK) activation is markedly sustained in p62dok−/− cells after the removal of growth factor. However, p62dok inactivation does not affect DNA damage and growth factor deprivation–induced apoptosis. Furthermore, p62dok inactivation causes a significant shortening in the latency of the fatal myeloproliferative disease induced by retroviral-mediated transduction of p210bcr-abl in bone marrow cells. These data indicate that p62dok acts as a negative regulator of growth factor–induced cell proliferation, at least in part through downregulating Ras/MAPK signaling pathway, and that p62dok can oppose leukemogenesis by p210bcr-abl.

scholarly journals Stimulation of Neural Stem Cell Proliferation by Inhibition of Phosphodiesterase 5

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Ana I. Santos ◽  
Bruno P. Carreira ◽  
Rui J. Nobre ◽  
Caetana M. Carvalho ◽  
Inês M. Araújo
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Soluble Guanylyl Cyclase ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mammalian Brain ◽  
Pde5 Inhibitors ◽  
Mitogen Activated Protein ◽  
Phosphodiesterase 5

The involvement of nitric oxide (NO) and cyclic GMP (cGMP) in neurogenesis has been progressively unmasked over the last decade. Phosphodiesterase 5 (PDE5) specifically degrades cGMP and is highly abundant in the mammalian brain. Inhibition of cGMP hydrolysis by blocking PDE5 is a possible strategy to enhance the first step of neurogenesis, proliferation of neural stem cells (NSC). In this work, we have studied the effect on cell proliferation of 3 inhibitors with different selectivity and potency for PDE5, T0156, sildenafil, and zaprinast, using subventricular zone-(SVZ-) derived NSC cultures. We observed that a short- (6 h) or a long-term (24 h) treatment with PDE5 inhibitors increased SVZ-derived NSC proliferation. Cell proliferation induced by PDE5 inhibitors was dependent on the activation of the mitogen-activated protein kinase (MAPK) and was abolished by inhibitors of MAPK signaling, soluble guanylyl cyclase, and protein kinase G. Moreover, sildenafil neither activated ERK1/2 nor alteredp27Kip1levels, suggesting the involvement of pathways different from those activated by T0156 or zaprinast. In agreement with the present results, PDE5 inhibitors may be an interesting therapeutic approach for enhancing the proliferation stage of adult neurogenesis.

scholarly journals Shp2–Mitogen-Activated Protein Kinase Signaling Drives Proliferation during Zebrafish Embryo Caudal Fin Fold Regeneration

2017 ◽  
Vol 38 (4) ◽  
Author(s):  
Alexander James Hale ◽  
Jeroen den Hertog
Keyword(s):  
Cell Proliferation ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Zebrafish Embryo ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Zebrafish Embryos ◽  
Caudal Fin ◽  
Mitogen Activated Protein ◽  
Wound Epidermis

ABSTRACT Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a −/− ptpn11b −/− zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin folds. Rescue experiments indicated that Shp2a has a functional signaling role, requiring its catalytic activity and SH2 domains but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin fold regeneration to similar extents. Expression of mmp9 and junbb , indicative of formation of the wound epidermis and distal blastema, respectively, suggested that these processes occurred in ptpn11a −/− ptpn11b −/− zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a–mitogen-activated protein kinase (MAPK) signaling in promoting cell proliferation during zebrafish embryo caudal fin fold regeneration.

scholarly journals Anti-Inflammatory Effects of Acupuncture at ST36 Point: A Literature Review in Animal Studies

2022 ◽  
Vol 12 ◽  
Author(s):  
Ji-Eun Oh ◽  
Seung-Nam Kim
Keyword(s):  
Animal Studies ◽  
Macrophage Polarization ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Clinical Benefits ◽  
Anti Inflammatory ◽  
Regulatory Effects ◽  
Underlying Mechanisms ◽  
Specific Acupoint

So far, a number of acupuncture studies have shown anti-inflammatory effects of acupuncture treatment, mostly known at specific point ST36. However, there is no literature that oversaw the inflammation-regulatory effects of acupuncture in each tissue. Therefore, we investigated how acupuncture at specific acupoint ST36 regulates inflammation and its underlying mechanisms. We searched literatures on PubMed until July 2021 using the keywords “animal, acupuncture, ST36, inflammation, immune,” and 292 literatures were searched. We ultimately selected 69 studies to determine the anti-inflammatory actions of acupuncture at ST36 and classified the changes of inflammatory mediators according to target regions. Forty-three studies were included in body fluids, 27 studies in the digestive system, 17 studies in the nervous system, and 30 studies in other tissues or organs. In this review, we found that acupuncture at ST36 has clinical benefits in relieving inflammation through several mechanisms such as vagus nerve activation, toll-like receptor 4 (TLR4)/NF-κB signaling, macrophage polarization, mitogen-activated protein kinase (MAPK) signaling pathway, and cholinergic anti-inflammatory pathway. We expect that these data will inform further studies related to ST36 acupuncture on inflammation.

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