scholarly journals Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Bao-Long Pan ◽  
Zong-Wu Tong ◽  
Shu-De Li ◽  
Ling Wu ◽  
Jun-Long Liao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Structural Damage ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Bone Diseases ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Osteoblast Proliferation ◽  
Proliferation And Differentiation

Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.

scholarly journals Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Shan Lei ◽  
Zhiwei He ◽  
Tengxiang Chen ◽  
Xingjun Guo ◽  
Zhirui Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Potential Biomarker

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

Inhibition of miR-200c Expression Promotes Activation of Extracellular Signal-Regulated Kinase (ERK)/ Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway and Inhibits Osteogenic Differentiation in Osteoporosis Mice

2020 ◽  
Vol 10 (2) ◽  
pp. 163-168
Author(s):  
Sheng Wang ◽  
Zhonghan Min ◽  
Run Gu ◽  
Zhongwei Yu ◽  
Pingquan Chen ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Bone Diseases ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Erk Mapk ◽  
Mitogen Activated Protein ◽  
Marrow Mesenchymal Stem Cells ◽  
Sirna Group

During OP bone metabolism, activated MAPK signaling can promote the proliferation and differentiation of osteoclasts. miRNAs involve in bone diseases. Our study aimed to evaluate miR-200c’s effect on ERK/MAPK signaling pathway in OP. miR-200c expression in OP mice and normal mice was detected by qPCR. BMSCs were cultured and transfected with siRNA to establish a miR-200c knockout model. Flow cytometry was used to detect cell apoptosis and ERK/MAPK signaling protein was detected by Western blot. miR-200c expression in OP mice was significantly lower than that in normal mice. Bone marrow mesenchymal stem cells (BMSCs) contain a large amount of siRNA particles under a fluorescence microscope. siRNA transfection can effectively inhibit miR-200c expression without difference of BMSCs apoptosis between miR-200c siRNA group and NC group. However, ERK1/2 and P38 expression in experimental group were significantly higher than those in NC siRNA group with reduced ALP activity. In addition, BMSCs osteogenic differentiation was further diminished when miR-200c expression was inhibited. miR-200c expression is lower in OP mice. miR-200c siRNA inhibits BMSCs osteogenic differentiation via ERK/MAPK signaling, thereby promoting OP progression.

scholarly journals Cardiovascular protective effects of GLP-1:A focus on the MAPK signaling pathway

2021 ◽  
Author(s):  
Yu-Yan Zhao ◽  
Lin-Hui Chen ◽  
Liang Huang ◽  
Yong-Zhen Li ◽  
Chen Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Mapk Pathway ◽  
Signal Transduction Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Glucagon Like Peptide 1 ◽  
Common Signal

Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by ileal endocrine that is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects through regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cell physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD), and discuss how GLP-1 exerts cardiovascular protective effects through MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular level. A better understanding of MAPK signaling pathway that are disregulated in CVD may aid in the design and development of promising GLP-1RA.

scholarly journals Disorder of sex development 46,XY associated with mutations in the gene MAP3K1. The report of clinical cases

2018 ◽  
Vol 64 (1) ◽  
pp. 45-49
Author(s):  
Irina V. Kopylova ◽  
Elena S. Kuznetsova ◽  
Igor S. Chugunov ◽  
Elizaveta M. Orlova ◽  
Oleg S. Danilenko ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Pathway ◽  
Disorders Of Sex Development ◽  
Sporadic Case ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Human Testis ◽  
Sex Development ◽  
Sex Inversion

The disorders of sex development (DSD) 46,XY may be caused by mutations in a number of genes involved in the gonadal differentiation. The XY sex inversion can be also due to disturbances at the level of mitogen-activated protein kinase (MAPK) kinase kinase 1 gene (MAP3K1) and MAPK-signaling pathway. During the last decade, the involvement of the MAPK pathway in the SRY gene up-regulation during the formation of male gonadal sex in mammals has been demonstrated. The role of MAPK-signaling pathway in the human sex determination is not fully understood. Probably, MAP3K1 and the MAPK-signaling pathway are one of the genetic pathways controlling normal development of human testis. So far, several families and sporadic cases of 46,XY DSD due to mutations in MAP3K1 gene have been reported in the literature. Clinical presentation of DSD in these patients varies from female phenotype with normal externalia to male phenotype with hypospadias. We describe rare cases of the DSD 46,XY (a family case of DSD in uterine sisters and a sporadic case) with mutations in the MAP3K1 gene that haven’t been previously described. The article also presents brief literature review on this pathology.

scholarly journals Antiprolactinoma Effect of Hordenine by Inhibiting MAPK Signaling Pathway Activation in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiong Wang ◽  
Run-zhu Guo ◽  
Li Ma ◽  
Qiao-yan Ding ◽  
Jun-hua Meng ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Interleukin 1 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Activation ◽  
Mitogen Activated Protein ◽  
Jnk Activation

Prolactinomas are harmful to human health, and the clinical first-line treatment drug is bromocriptine. However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen-activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats.

scholarly journals Disorder of sex development 46,XY associated with mutations in the gene MAP3K1. The report of clinical cases

2018 ◽  
Vol 64 (1) ◽  
pp. 45-49
Author(s):  
Irina V. Kopylova ◽  
Elena S. Kuznetsova ◽  
Igor S. Chugunov ◽  
Elizaveta M. Orlova ◽  
Oleg S. Danilenko ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Pathway ◽  
Disorders Of Sex Development ◽  
Sporadic Case ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Human Testis ◽  
Sex Development ◽  
Sex Inversion

The disorders of sex development (DSD) 46,XY may be caused by mutations in a number of genes involved in the gonadal differentiation. The XY sex inversion can be also due to disturbances at the level of mitogen-activated protein kinase (MAPK) kinase kinase 1 gene (MAP3K1) and MAPK-signaling pathway. During the last decade, the involvement of the MAPK pathway in the SRY gene up-regulation during the formation of male gonadal sex in mammals has been demonstrated. The role of MAPK-signaling pathway in the human sex determination is not fully understood. Probably, MAP3K1 and the MAPK-signaling pathway are one of the genetic pathways controlling normal development of human testis. So far, several families and sporadic cases of 46,XY DSD due to mutations in MAP3K1 gene have been reported in the literature. Clinical presentation of DSD in these patients varies from female phenotype with normal externalia to male phenotype with hypospadias. We describe rare cases of the DSD 46,XY (a family case of DSD in uterine sisters and a sporadic case) with mutations in the MAP3K1 gene that haven’t been previously described. The article also presents brief literature review on this pathology.

The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Valérie Marin ◽  
Catherine Farnarier ◽  
Sandra Grès ◽  
Solange Kaplanski ◽  
Michael S.-S. Su ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Endothelial Activation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Chemokine Production ◽  
Mitogen Activated Protein

Abstract Thrombin, the terminal serine protease in the coagulation cascade, is a proinflammatory molecule in vivo and induces endothelial activation in vitro. The cellular signaling mechanisms involved in this function are unknown. The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin-induced chemokine production was studied. Phosphorylation of both p38 MAPK and its substrate, ATF-2, was observed in human umbilical vein endothelial cells (HUVECs) stimulated with thrombin, with a maximum after 5 minutes of stimulation. Using the selective p38 MAPK inhibitor SB203580, there was a significant decrease in thrombin-induced interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) protein production and messenger RNA steady-state levels. In addition, SB203580 decreased IL-8 and MCP-1 production induced by the thrombin receptor-1 agonist peptide (TRAP), suggesting functional links between the thrombin G protein–coupled receptor and the p38 MAPK pathway. Furthermore, endothelial activation in the presence of SB203580 decreased the chemotactic activity of thrombin-stimulated HUVEC supernatant on neutrophils and monocytic cells. In contrast, the p42/p44 MAPK pathway did not appear to be involved in thrombin- or TRAP-induced endothelial chemokine production, because there was no reduction in the presence of the p42/p44-specific inhibitor PD98059. These results demonstrate that the p38 rather than p42/44 MAPK signaling pathway plays an important role in thrombin-induced endothelial proinflammatory activation and suggest that inhibition of p38 MAPK may be an interesting target for anti-inflammatory strategies in vascular diseases combining thrombosis and inflammation.

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

scholarly journals The oxygenated products of cryptotanshinone by biotransformation with Cunninghamella elegans exerting anti-neuroinflammatory effects by inhibiting TLR 4-mediated MAPK signaling pathway

2020 ◽  
Author(s):  
Jing-Shuai Wu ◽  
Qin-Yu Meng ◽  
Xiao-Hui Shi ◽  
Zhen-Kun Zhang ◽  
Hua-Shi Guan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transcriptome Analysis ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cunninghamella Elegans ◽  
Chinese Medicinal Herb ◽  
Oxygenated Products

Abstract Background: Neuroinflammatory processes are critical in the development and progression of Alzheimer's disease (AD). The potent anti-neuroinflammatory inhibitors are expected as the candidates to treat AD. Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities, especially anti-oxidation and anti-inflammation. Methods: Cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028 to improve its bioactivities and physicochemical properties. The structures of transformed products were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. Their anti-neuroinflammatory activities were assessed by ELISA, transcriptome analysis, western blot, and immunofluorescence methods. Results: Three oxygenated products (2–4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. All of the biotransformed products (2–4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16‒1.16 μM, approximately 2‒20 folds stronger than the substrate (1). These biotransformed products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. Conclusion: The biotransformed products of cryptotanshinone exhibit potent anti-neuroinflammatory activities. These findings provide a basal material for the discovery of candidates in treating AD.

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