scholarly journals 17β-Estradiol attenuates p38MAPK activity but not PKCα induced by angiotensin II in the brain

2019 ◽  
Vol 240 (2) ◽  
pp. 345-360 ◽  
Author(s):  
G Almeida-Pereira ◽  
T Vilhena-Franco ◽  
R Coletti ◽  
S Q Cognuck ◽  
H V P Silva ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Sodium Intake ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Mapk Signaling ◽  
Cellular Mechanisms ◽  
Ovx Rats ◽  
17Β Estradiol

17β-Estradiol (E2) has been shown to modulate the renin–angiotensin system in hydromineral and blood pressure homeostasis mainly by attenuating angiotensin II (ANGII) actions. However, the cellular mechanisms of the interaction between E2 and angiotensin II (ANGII) and its physiological role are largely unknown. The present experiments were performed to better understand the interaction between ANGII and E2 in body fluid control in female ovariectomized (OVX) rats. The present results are the first to demonstrate that PKC/p38 MAPK signaling is involved in ANGII-induced water and sodium intake and oxytocin (OT) secretion in OVX rats. In addition, previous data from our group revealed that the ANGII-induced vasopressin (AVP) secretion requires ERK1/2 signaling. Therefore, taken together, the present observations support a novel concept that distinct intracellular ANGII signaling gives rise to distinct neurohypophyseal hormone release. Furthermore, the results show that E2 attenuates p38 MAPK phosphorylation in response to ANGII but not PKC activity in the hypothalamus and the lamina terminalis, suggesting that E2 modulates ANGII effects through the attenuation of the MAPK pathway. In conclusion, this work contributes to the further understanding of the interaction between E2 and ANGII signaling in hydromineral homeostasis, as well as it contributes to further elucidate the physiological relevance of PKC/p38 MAPK signaling on the fluid intake and neurohypophyseal release induced by ANGII.

The defense response of Caenorhabditis elegans to Cutibacterium acnes SK137 via the TIR-1-p38 MAPK signaling pathway

2021 ◽  
Author(s):  
Ayano Tsuru ◽  
Yumi Hamazaki ◽  
Shuta Tomida ◽  
Mohammad Shaokat Ali ◽  
Eriko Kage-Nakadai
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Defense Response ◽  
Mapk Pathway ◽  
Defense Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Healthy Skin ◽  
Cutibacterium Acnes

Abstract Cutibacterium acnes plays roles in both acne disease and healthy skin ecosystem. We observed that mutations in the tir-1/SARM1 and p38 MAPK cascade genes significantly shortened Caenorhabditis elegans lifespan upon Cutibacterium acnes SK137 infection. Antimicrobial molecules were induced by SK137 in a TIR-1-dependent manner. These results suggest that defense responses against SK137 involve the TIR-1-p38 MAPK pathway in Caenorhabditis elegans.

Long non-coding RNA H19 acts as a microRNA-194 sponge to inhibit the apoptosis and promote the proliferation of hypertrophic scar fibroblasts

2021 ◽  
Author(s):  
Bo Liu ◽  
Lijuan Lin ◽  
Shengjin Yu ◽  
Rongjun Xia ◽  
Linlin Zheng
Keyword(s):  
P38 Mapk ◽  
Hypertrophic Scar ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Hypertrophic Scars ◽  
Downstream Effector ◽  
Non Coding Rna ◽  
Proliferation And Apoptosis ◽  
Signaling Axis ◽  
Underlying Mechanisms

The effects of long non-coding RNAs (lncRNAs) on the proliferation of hypertrophic scars have been described. However, the underlying mechanisms are not well characterized. The present study aimed to investigate the mechanisms of lncRNA H19 in hypertrophic scars. The effects of the lncRNA H19 on the proliferation and apoptosis of hypertrophic scar fibroblasts (HSFs) were analyzed using 5’-Ethynyl-2’-deoxyuridine staining, flow cytometry, and MTT. The results revealed H19 promoted the proliferation and inhibited the apoptosis in HSF. In addition, the binding associations between H19 and microRNA-194 (miR-194), and miR-194 and insulin-like growth factor-I receptor (IGF1R) were identified using bioinformatics screening and verified using dual-luciferase assays. Furthermore, the effects of the IGF1R knockdown on H19-induced HSF phenotypes and regulation over the p38 MAPK pathway were determined. Mechanistically, miR-194 was identified as the downstream effector of the H19-mediated phenotypes of HSFs through its ability to directly target IGF1R, thus modulating the p38 MAPK signaling pathway. In conclusion, the findings suggested that H19 may inhibit the apoptosis and promote the proliferation of HSFs through the miR-194/IGF1R/p38 MAPK signaling axis, thereby contributing to the progression of hypertrophic scars. These findings may provide novel targets for the treatment of hypertrophic scars.

scholarly journals APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway

2011 ◽  
Vol 300 (1) ◽  
pp. E103-E110 ◽  
Author(s):  
Xiaoban Xin ◽  
Lijun Zhou ◽  
Caleb M. Reyes ◽  
Feng Liu ◽  
Lily Q. Dong
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Adaptor Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Mapk Activation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein

The adaptor protein APPL1 mediates the stimulatory effect of adiponectin on p38 mitogen-activated protein kinase (MAPK) signaling, yet the underlying mechanism remains unclear. Here we show that, in C2C12 cells, overexpression or suppression of APPL1 enhanced or suppressed, respectively, adiponectin-stimulated p38 MAPK upstream kinase cascade, consisting of transforming growth factor-β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase 3 (MKK3). In vitro affinity binding and coimmunoprecipitation experiments revealed that TAK1 and MKK3 bind to different regions of APPL1, suggesting that APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation. Interestingly, suppressing APPL1 had no effect on TNFα-stimulated p38 MAPK phosphorylation in C2C12 myotubes, indicating that the stimulatory effect of APPL1 on p38 MAPK activation is selective. Taken together, our study demonstrated that the TAK1-MKK3 cascade mediates adiponectin signaling and uncovers a scaffolding role of APPL1 in regulating the TAK1-MKK3-p38 MAPK pathway, specifically in response to adiponectin stimulation.

scholarly journals Adenosine pretreatment attenuates angiotensin II-mediated p38 MAPK activation in a protein kinase A dependent manner

2010 ◽  
Vol 4 (5) ◽  
pp. 721-729
Author(s):  
Hamid Yaghooti ◽  
Mohsen Firoozrai ◽  
Soudabeh Fallah ◽  
Mohammad Reza Khorramizadeh
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
P38 Mapk ◽  
Inflammatory Mediators ◽  
Endothelial Permeability ◽  
Renin Angiotensin System ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Kinase A

Abstract Background: Adenosine is known as a protective and anti-inflammatory nucleoside. Angiotensin II is the main hormone of the renin-angiotensin system. It is associated with endothelial permeability, recruitment, and activation of the immune cells through induction of inflammatory mediators. Matrix metalloproteinase-9 (MMP-9) plays an important role in inflammatory processes mediated by macrophages. Objectives: Investigate whether adenosine pretreatment modulates angiotensin II-induced MMP-9 expression and activation of signaling molecules. Methods: Human monocytic U-937 cells were treated with either adenosine or angiotensin II alone or angiotensin II following a pretreatment with adenosine. Supernatants were analyzed for MMP-9 activity by zymography method. MMP-9 gene expression was analyzed using real-time PCR. Activation of inflammatory mediators IκB-α, NF-κB, JNK, p38 MAPK, and STAT3 were analyzed by a multi-target ELISA kit. Association of Protein kinase A (PKA) in adenosine effects was studied by pre-incubation with H89, a selective PKA inhibitor. Results: Treatment of the cells with angiotensin II significantly increased MMP-9 production (p <0.05). Adenosine pretreatment did not attenuate this angiotensin II effect. Angiotensin II treatment induced NF-κB, JNK and p38 activation. Pretreatment with adenosine prior to angiotensin II stimulation showed a 40% inhibitory effect on p38 induction (p <0.05). This effect was reversed by PKA inhibition. Conclusion: The present data confirmed that monocytic MMP-9 was a target gene for angiotensin II. Adenosine pretreatment did not inhibit MMP-9 increase in response to angiotensin II. However, it showed a potential inhibitory effect on angiotensin II inflammatory signaling.

scholarly journals Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

2016 ◽  
Vol 39 (6) ◽  
pp. 2216-2226 ◽  
Author(s):  
Pei Li ◽  
Yuan Xu ◽  
Yibo Gan ◽  
Liyuan Wang ◽  
Bin Ouyang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Matrix Synthesis ◽  
P38 Mapk Pathway ◽  
Collagen Ii

Background/Aims: Matrix homeostasis within the disc nucleus pulposus (NP) tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17β-estradiol (E2) in NP matrix synthesis and its underlying mechanism. Methods: Rat NP cells were cultured with (10-5, 10-7 and 10-9 M) or without (control) E2 for48 hours. The estrogen receptor (ER)-β antagonist PHTPP and ERβ agonist ERB 041 were used to investigate the role mediated by ERβ. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG) content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. Results: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. Conclusion: E2 can enhance matrix synthesis of NP cells and the ERβ/p38 MAPK pathway is involved in this regulatory process.

17β-Estradiol induces odontoblastic differentiation via activation of the c-Src/MAPK pathway in human dental pulp cells

2015 ◽  
Vol 93 (6) ◽  
pp. 587-595 ◽  
Author(s):  
Su Mi Woo ◽  
Kyung Joo Seong ◽  
Sang Jin Oh ◽  
Hong Ju Park ◽  
Sun Hun Kim ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Dental Pulp Cells ◽  
Human Dental Pulp Cells ◽  
Odontoblastic Differentiation ◽  
Alp Activity ◽  
Human Dental Pulp ◽  
Pulp Cells ◽  
17Β Estradiol

The present study is aimed at investigating the effects of the exogenous estrogen 17β-estradiol (E2) on odontoblastic differentiation in human dental pulp cells (HDPCs) immotalized with hTERT gene and their molecular mechanism. Proliferation was detected by BrdU assay, and odontoblast differentiation induction was evaluated by the expression of dentin sialophosphoprotein (DSPP), dentin sialoprotein (DSP) and dentin matrix protein1 (DMP1), and alkaline phosphatase (ALP) activity and mineralization. Estrogen receptor-α (ER-α), c-Src, and mitogen-activated protein kinases (MAPKs) were examined and their inhibitors were used to determine the roles on odontogenic induction. E2 significantly promoted the HDPC proliferation, which was mediated by extracellular signal-related kinase 1/2. E2 upregulated DSPP, DSP, and DMP1 as the odontogenic differentiation markers and enhanced ALP activity and mineralization. E2 increased phosphorylation of ER-α and fulvestrant, an ER downregulator, significantly downregulated DSPP, DMP1, and DSP induced by E2. Moreover, E2 treatment activated c-Src and MAPKs upon odontogenic induction, whereas chemical inhibition of c-Src and MAPKs decreased expression of DSPP, DMP1, and DSP and mineralization augmented by E2. Moreover, fulvestrant reduced E2-induced phosphorylation of c-Src and MAPK and inhibition of c-Src by PP2 attenuated activation of MAPKs during E2-induced odontoblastic differentiation. Taken together, these results indicated that E2 stimulates odontoblastic differentiation of HDPCs via coordinated regulation of ER-α, c-Src, and MAPK signaling pathways, which may play a key role in the regeneration of dentin.

Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

2007 ◽  
Vol 293 (4) ◽  
pp. H2537-H2542 ◽  
Author(s):  
David W. Stepp ◽  
Erika I. Boesen ◽  
Jennifer C. Sullivan ◽  
James D. Mintz ◽  
Clark D. Hair ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zucker Rats ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Insulin Resistant

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.

scholarly journals Interleukin-33 promotes type 1 cytokine expression via p38 MAPK in human natural killer cells

2019 ◽  
Author(s):  
David E. Ochayon ◽  
Ayad Ali ◽  
Pablo C. Alarcon ◽  
Durga Krishnamurthy ◽  
Leah C. Kottyan ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Cytokine Expression ◽  
Chronic Obstructive ◽  
Interleukin 33 ◽  
Ifn Γ

This study tests the hypothesis that activation of mitogen-activated protein kinase (MAPK) by physiologically-relevant concentrations of interleukin-33 (IL-33) contributes to enhanced cytokine expression by IL-12 stimulated human natural killer (NK) cells. While IL-33 canonically triggers type 2 cytokine responses, this cytokine can also synergize with type 1 cytokines like IL-12 to provoke interferon-gamma (IFN-γ). We show that picogram concentrations of IL-12 and IL-33 are sufficient to promote robust secretion of IFN-γ by human NK cells that greatly exceeds responses to either cytokine alone. Nanogram doses of IL-33, potentially consistent with levels in tissue microenvironments, synergize with IL-12 to induce secretion of additional cytokines, including tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-33-induced activation of the p38 MAPK pathway in human NK cells is crucial for enhanced release of IFN-γ and TNF in response to IL-12. Mechanistically, IL-33-induced p38 MAPK signaling enhances stability of IFNG transcripts and triggers ADAM17-mediated cleavage of TNF from the cell surface. These data support our hypothesis and suggest that altered sensitivity of NK cells to IL-12 in the presence of IL-33 may have important consequences in diseases associated with mixed cytokine milieus, like asthma and chronic obstructive pulmonary disease.Graphical Abstract

scholarly journals Exosomes Derived from Dental Pulp Stem Cells Accelerate Cutaneous wound Healing by Enhancing Angiogenesis via Cdc42/p38 MAPK Pathway

2021 ◽  
Author(s):  
Ziyu Zhou ◽  
Jianmao Zheng ◽  
Danle Lin ◽  
Yanan Chen ◽  
Xiaoli Hu
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Dental Pulp ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Protein Levels

Abstract Background: Skin wound healing is a common challenging clinical problem and need advanced treatment strategies. Here, we investigated the therapeutic effects of exosomes derived from dental pulp stem cells (DPSC-Exos) on cutaneous wound healing and the underlying mechanisms. Methods: The effects of DPSC-Exos on cutaneous wound healing in mice were examined by measuring wound closure rates, histological and immunohistochemical analysis. A series of functional assays were performed to evaluate the effects of DPSC-Exos on the angiogenic activities of human umbilical vein endothelial cells (HUVECs) in vitro. TMT-based quantitative proteomic analysis of DPSCs and DPSC-Exos was performed. Gene ontology (GO) and KEGG pathway enrichment analysis were used to evaluate biological functions and pathways for the differentially expressed proteins in DPSC-Exos. Western blot was used to assess the protein levels of Cdc42 and p38 in DPSC-Exos-induced angiogenesis of HUVECs. SB203580, a p38 MAPK signaling pathway inhibitor, was employed to verify the role of p38 MAPK pathway in these processes.Results: Histological and immunohistochemical staining revealed that DPSC-Exos accelerated wound healing by improving neovascularization. DPSC-Exos augmented the migration, proliferation, and capillary formation capacity of HUVECs. Proteomic data demonstrated that proteins contained in DPSC-Exos regulated vasculature development and angiogenesis. Pathway analysis showed that proteins expressed in DPSC-Exos were involved in several pathways including MAPK pathway. Western blotting demonstrated that DPSC-Exos increased the protein levels of Cdc42 and phosphorylation of p38 in HUVECs. SB203580 suppressed the angiogenesis of HUVECs induced by DPSC-Exos.Conclusions: DPSC-Exos could accelerate cutaneous wound healing by enhancing the angiogenic properties of HUVECs via Cdc42/p38 MAPK signaling pathway.

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