scholarly journals The mechanism of TDP‐43 gene expression on inflammatory factors and the JNK and p38 MAPK signalling pathways in ischaemic hypoxic stress dependence

2019 ◽  
Vol 16 (3) ◽  
pp. 724-729 ◽  
Author(s):  
He Huang ◽  
Zhao‐Fei Zhang ◽  
Feng‐Wei Qin ◽  
Wang Tang ◽  
Dong‐Hua Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
P38 Mapk ◽  
Inflammatory Factors ◽  
Signalling Pathways ◽  
Hypoxic Stress ◽  
Stress Dependence ◽  
Mapk Signalling

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

scholarly journals trans-Cinnamic acid, but not p-coumaric acid or methyl cinnamate, induces fibroblast migration through PKA- and p38-MAPK signalling pathways

2021 ◽  
Author(s):  
Fernanda Lima Torres de Aquino ◽  
Juliane Pereira da Silva ◽  
Jamylle Nunes de Souza Ferro ◽  
Vincent Lagente ◽  
Emiliano Barreto
Keyword(s):  
P38 Mapk ◽  
Cinnamic Acid ◽  
Signalling Pathways ◽  
Coumaric Acid ◽  
Methyl Cinnamate ◽  
Fibroblast Migration ◽  
Mapk Signalling

LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway

2019 ◽  
Vol 41 (9) ◽  
pp. 1273-1281 ◽  
Author(s):  
Kai Fang ◽  
Caixia Hu ◽  
Xiufen Zhang ◽  
Yafei Hou ◽  
Danfeng Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
P38 Mapk ◽  
The Cancer Genome Atlas ◽  
Mitogen Activated Protein Kinase ◽  
High Expression ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Mapk Signalling ◽  
And Migration

Abstract Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

scholarly journals Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes

2015 ◽  
Vol 37 (2) ◽  
pp. 697-706 ◽  
Author(s):  
Pengfei Hu ◽  
Hui Zhou ◽  
Ming Lu ◽  
Liping Dou ◽  
Gang Bo ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Treated Group ◽  
Protective Role ◽  
Signalling Pathways ◽  
Control Group ◽  
Advanced Glycation ◽  
Rat Cardiomyocytes ◽  
Advanced Glycation End Product ◽  
Mapk Signalling ◽  
Induced Apoptosis

Background/Aims: To investigate the effect of advanced glycation endproduct-induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis. Methods: After cultured rat cardiomyocytes were treated with advanced glycation end products (AGEs), protein expression was detected by western blotting, autophagosomes were observed by electron microscopy, the cell apoptotic rate was determined by flow cytometry, and cell variability was quantified by the MTT assay. Results: After cultured cardiomyocytes were treated with AGEs, the level of autophagy-associated protein LC3-II was up-regulated and SQSTM1/p62 was down-regulated; the number of autophagosomes was increased. Compared with the control group, the apoptotic rate of cardiomyocytes increased, and the cardiomyocyte viability was decreased in the AGE-treated group. Furthermore, pretreating cells with3-MA, an autophagy inhibitor, could enhance these effects. Treatment with AGEs activated phospho-ERK, phospho-JNK, and phospho-p38/MAPK but inhibited phospho-Akt and phospho-mTOR. Pretreatment with an ERK inhibitor and an Akt activator could inhibit AGE-induced autophagy, demonstrating that AGEs induce autophagy in cardiomyocytes through the ERK and Akt signalling pathways. Conclusion: AGEs can induce autophagy through the PI3K/AKT/mTOR and ERK signalling pathways and induce apoptosis through the PI3K/AKT/mTOR and p38/MAPK signalling pathways in rat cardiomyocytes. Autophagy plays a protective role in AGE-induced apoptosis in cardiomyocytes.

Antagonistic roles of the ERK and p38 MAPK signalling pathways in globin expression, haem biosynthesis and iron uptake1

2010 ◽  
Vol 432 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Louay Mardini ◽  
Jadwiga Gasiorek ◽  
Anna Derjuga ◽  
Lucie Carrière ◽  
Matthias Schranzhofer ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Iron Uptake ◽  
Mapk Pathway ◽  
Globin Gene ◽  
Erythroid Differentiation ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Erythroid Cells ◽  
Mapk Signalling ◽  
Haem Biosynthesis

Late-stage erythroid cells synthesize large quantities of haemoglobin, a process requiring the co-ordinated regulation of globin and haem synthesis as well as iron uptake. In the present study, we investigated the role of the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) signalling pathways in MEL (mouse erythroleukaemia) cell differentiation. We found that treatment of HMBA (hexamethylene bisacetamide)-induced MEL cells with the ERK pathway inhibitor UO126 results in an increase in intracellular haem and haemoglobin levels. The transcript levels of the genes coding for βmajor-globin, the haem biosynthesis enzyme 5-aminolevulinate synthase 2 and the mitochondrial iron transporter mitoferrin 1 are up-regulated. We also showed enhanced expression of globin and transferrin receptor 1 proteins upon UO126 treatment. With respect to iron uptake, we found that ERK inhibitor treatment led to an increase in both haem-bound and total iron. In contrast, treatment of MEL cells with the p38 MAPK pathway inhibitor SB202190 had the opposite effect, resulting in decreased globin expression, haem synthesis and iron uptake. Reporter assays showed that globin promoter and HS2 enhancer-mediated transcription was under the control of MAPKs, as inhibition of the ERK and p38 MAPK pathways led to increased and decreased gene activity respectively. Our present results suggest that the ERK1/2 and p38α/β MAPKs play antagonistic roles in HMBA-induced globin gene expression and erythroid differentiation. These results provide a novel link between MAPK signalling and the regulation of haem biosynthesis and iron uptake in erythroid cells.

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