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Substrate Stiffness Affects Endothelial Cell Junctions and mapk signaling pathway

Journal of Biosciences and Medicines 2022年第2期10卷 124-135页

作者： Huanli Wang Chao Zhang Xiaomei Han Jin Xu Yue Zhou School of Biomedical Engineering Shanghai Jiao Tong University Shanghai China

Vascular homeostasis is critical for maintaining normal vascular structure and function. Aging is an irreversible trigger of vascular sclerosis, which causes structural and functional damage to blood vessels, leading to severe atherosclerosis. Endothelial cells (ECs) can respond to mechanical stimuli from the extracellular matrix, causing disruption of endothelial barrier function and activating signaling pathways to regulate cellular behavior under pathological conditions. In this paper, we investigated the effect of substrate stiffness on endothelial cell junctions, and the activation of mitogen-activated protein kinase (mapk) signaling pathways. An in vitro stiffness model was established using polyacrylamide hydrogels of 1 kPa, 20 kPa and 100 kPa. By transcriptome analysis, we found that the cell-cell junction, cadherin binding, cytoskeleton and classical signaling pathways such as mapk and Rho GTPase of endothelial cells were regulated by substrate stiffness. The expression of cell junction-related molecules TJP1, TJP2, JAM3 and JCAD was also found to be reduced at higher stiffness. The mapk signaling pathway-related molecules MAP2K3, MAP2K7, MAP3K3, MAP3K6, mapk3, mapk7 were upregulated with increased stiffness. qRT-PCR analysis showed that the gene expression of JCAD was reduced with increased stiffness. Immunofluorescence staining of VE-cadherin indicated that the total fluorescence level of VE-cadherin decreased significantly with increased stiffness, and stiffness impaired the cell-cell junction with increased punctuation and discontinuity. Western blotting analysis confirmed that the protein expression ratio of pp38mapk/p38mapk increased with stiffness. Our research suggested that substrate stiffness played an important role in regulating endothelial cell integrity and mapk signaling pathway.

关键词： Substrate Stiffness Endothelial Cell Cell Junction mapk signaling pathway

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DAP inhibits inflammatory response of TNF-α-induced by modulating the mapk signaling pathway in synovial cell

DAP inhibits inflammatory response of TNF-α-induced by modu...

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第十三届全国免疫学学术大会

作者： Nanzhen Kuang Jieying Wang Xiaoping Zeng Chan Dai Huimin Deng Youchang Hu Yingyuan Fu Department of Immunology School of Basic Medical Sciences Nanchang University

Daphnetin extracted from Daphne odora *** contains coumarin compounds, which has a good anti-inflammatory analgesic *** this study, we investigated whether Daphnetin can reduce the inflammatory response of TNF-α-induced by inhibiting mapk signaling pathway in synovial cell of CIA *** the model of synovial cells from CIA rats induced by TNF-α.The expression of inflammatory cytokines in synovial cells of CIA rats was observed by real-time PCR and *** expression of mapk signal pathway protein and nuclear translocation was detected by western blot and immunofluorescence *** results show, The levels of IL-6, TGF-β, MMP-3 and MMP-13 mRNA in IL-6, TGF-β, MMP-3 and MMP-13 were significantly lower than those in the culture supernatant Model control group;The expression of p38, ERK1/2, JNK protein in synovial cells of CIA rats induced by TNF-α decreased the expression of p-p38, p-ERK1/2 and p-JNK in the *** conclusion, daphnetin can affect the activation of mapk signaling pathway and reduce the expression of inflammatory factors throgh inhibiting the mapk signaling pathway, play the role of anti-rheumatic inflammation.

关键词： Daphnetin synovial cells mapk signaling pathway

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Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and mapk signaling pathways in Spontaneous Hypertensive Rats

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Chinese Journal of Integrative Medicine 2022年第4期28卷 357-365页

作者： CHEN Xin-yu YANG Lu-ping ZHENG Ya-ling LI Yu-xi ZHONG Dong-ling JIN Rong-jiang LI Juan School of Health Preservation and Rehabilitation Chengdu University of Traditional Chinese MedicineChengdu610072China Food Science and Nutrition School University of LeedsLeedsLS29JTUK Department of Rehabilitation the Second People’s Hospital of ChengduChengdu610072China School of Acupuncture-Moxibustion and Tuina Chengdu University of Traditional Chinese MedicineChengdu610072China

Objective:To investigate whether the antihypertensive mechanism of electroacupuncture(EA)is associated with attenuating phenotype transformation of vascular smooth muscle cells(VSMCs)via phosphoinositide3-kinase(PI3K)/protein kinase B(Akt)and mitogen-activated protein kinase(mapk)signaling ***:Eight Wistar-ktoyo(WKY)rats were set as normal blood pressure group(normal group).A total of 32 spontaneous hypertensive rats(SHRs)were randomly divided into 4 groups using random number tables:a model group,an EA group,an EA+PI3K antagonist group(EA+P group),and an EA+p38 mapk agonist+extracellular signal-regulated kinase(ERK)agonist group(EA+M group)(n=8/group).SHRs in EA group,EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks,while rats in the normal and model groups were bundled in same *** systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)of each rat was measured at 0 week and the 4th *** 4-week intervention,thoracic aorta was collected for hematoxylin-eosin(HE)staining,immunohistochemistry[the contractile markersα-smooth muscle actin(α-SMA)and calponin and the synthetic marker osteopontin(OPN)]and Western blot[α-SMA,calponin,OPN,PI3K,phosphorylated-Akt(p-Akt),Akt,p-p42/44 ERK,total p42/44 ERK,p-p38 mapk and total p38 mapk].Results:EA significantly reduced SBP,DBP and MAP(Pmapk decreased in EA group(Pmapk agonist and ERK ***:EA was an effective treatment for BP *** antihypertensive effect of EA may be rela

关键词： electroacupuncture hypertension vascular smooth muscle cells PI3K/Akt signaling pathway mapk signaling pathway

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BcSDR1 is involved in regulation of glucose transport and cAMP and mapk signaling pathways in Botrytis cinerea

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Journal of Integrative Agriculture 2022年第9期21卷 2628-2640页

作者： SI He-long ZHANG Kang LI Bai YUAN Xue-mei ZANG Jin-ping CAO Hong-zhe XING Ji-hong DONG Jin-gao State Key Laboratory of North China Crop Improvement and Regulation Hebei Agricultural UniversityBaoding 071000P.R.China Hebei Key Laboratory of Plant Physiology and Molecular Pathology Hebei Agricultural UniversityBaoding 071000P.R.China

Botrytis cinerea is a typical necrotrophic pathogenic fungus that causes severe diseases in a wide range of plant species, leading to significant economic losses. Our previous study showed that BcSDR1 positively regulates growth,development, and pathogenicity of B. cinerea. However, the regulation mechanism of BcSDR1 and the relationship between BcSDR1 and cAMP and mapk signaling pathways are not well understood. In this study, transcriptome data showed that BcSDR1 is involved in glucose transmembrane transport, signal transduction, secondary metabolism, and other biological processes. BcSDR1 mutant(BCt41) showed remarkably weak sensitivity to cAMP and mapk signaling pathways specific inhibitors, SQ22536 and U0126, and significantly decreased cAMP content. The key genes of cAMP and mapk signaling pathways, BcGB1, BcBTP1, BcBOS1, BcRAS1, and BcBMP3 were significantly upregulated,whereas BcPLC1, BcBCG1, BcCDC4, BcSAK1, BcATF1, and BcBAP1 were significantly downregulated(P<0.05).BcSDR1 was obviously upregulated in BcBCG2, BcBCG3, BcPKA1, and BcPKAR RNA interference(RNAi) mutants, but significantly downregulated in BcPKA2, BcBMP1, and BcBMP3 RNAi mutants. Thus, BcBCG2, BcBCG3, BcPKA1, and BcPKAR negatively regulate BcSDR1 expression, whereas BcPKA2, BcBMP1, and BcBMP3 positively regulate BcSDR1expression.

关键词： Botrytis cinerea BcSDR1 glucose transmembrane transport cAMP signaling pathway mapk signaling pathway

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Immunoregulatory polysaccharides from Apocynum venetum *** stimulate phagocytosis and cytokine expression via activating the NF-κB/mapk signaling pathways in RAW264.7 cells

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Food Science and Human Wellness 2022年第4期11卷 806-814页

作者： Honglin Wang Changyang Ma Dongxiao Sun-Waterhouse Jinmei Wang Geoffrey Ivan Neil Waterhouse Wenyi Kang National R&D Center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Functional Food Engineering Technology Research Center Kaifeng 475004China School of Chemical Sciences University of AucklandAuckland 1142New Zealand Joint International Research Laboratory of Food&Medicine Resource Function Kaifeng 475004China

Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cells. Both the level of released nitric oxide(NO) and expression of inducible nitric oxide synthase(iNOS) m RNA were significantly enhanced in the RAW264.7 macrophages cells treated by Vp2a-Ⅱ and Vp3. Vp2a-Ⅱ(100–800 μg/m L) and Vp3(400 μg/mL) could significantly increase the phagocytic activity of RAW264.7 cells and the secretion and m RNA expression of TNF-α and IL-6 in a concentrationdependent manner through affecting mitogen-activated protein kinase(mapk) activity and nuclear factor κB(NF-κB) nuclear translocation. Vp2a-Ⅱ might activate the mapk signaling pathways and induce the nuclear translocation of NF-κB p65, whilst Vp3 likely activated the NF-κB and mapk signaling pathways without influencing the p38 mapk route.

关键词： Apocynum venetum L.flowers Immunomodulatory polysaccharide RAW264.7 cells NF-κB signaling pathway mapk signaling pathway

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Pogostemon cablin essential oil as feed additive promotes the repair of the rumen epithelial barrier in heat-stressed beef cattle

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Animal Nutrition 2024年第3期18卷 433-440页

作者： Huan Chen Mingrui Yang Xianglong Shang Hao Chen Yi Li Yanjiao Li Lin Li Mingren Qu Xiaozhen Song Jiangxi Province Key Laboratory of Animal Nutrition Engineering Research Center of Feed DevelopmentJiangxi Agricultural UniversityNanchang 330045China

Pogostemon cablin essential oil(PEO),extracted from ***,has anti-oxidant,anti-inflammatory,and anti-stress properties,as well as the ability to improve gastrointestinal *** study aims to evaluate the effects of PEO on the performance,rumen epithelial morphology,and barrier function in heat-stressed beef ***-six male Jingjiang cattle at 18 months old were randomly assigned into four groups and fed a diet containing PEO at 0(control),50,100,or 150 mg/kg in the feed concentrate(n=9).All experimental cattle were fed under high temperature and humidity in summer for 60 *** results indicated that 50 mg/kg of PEO treatment enhanced the average daily gain of beef cattle compared with the control group(P=0.032).All PEO treatments reduced the diamine oxidase activity(P=0.004)and malondialdehyde content(P=0.008)in *** addition,the content of 70 kDa heat shock protein in the 100 mg/kg group was increased,and the activity of glutathione peroxidase and total antioxidant capacity in both 100 mg/kg and 150 mg/kg groups were enhanced compared to the control group(Psignaling pathway.

关键词： Beef cattle Heat stress Rumen epithelial barrier Pogostemon cablin essential oil Growth performance mapk signaling pathway

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Ethylene thiourea exposure induces neurobehavioral toxicity in zebrafish by disrupting axon growth and neuromuscular junctions

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Journal of Environmental Sciences 2024年第3期137卷 108-119页

作者： Jingming Wang Zhiquan Yu Yongfeng Wang Yuanyao Chen Lin Xiao Yanjun Zong Qiyuan Feng Lianqi Peng Huiping Zhang Chunyan Liu Institute of Reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Ethylene thiourea(ETU)converted from ethylene bisdithiocarbamate(EBDC)fungicides has aroused great concern because of its prevalence and harmful *** ETU-induced neurotoxicity has been reported,the potential mechanisms remain *** study provided insights into its neurotoxic effects at environmentally relevant concentrations in *** findings showed that embryonic exposure to ETU decreased the hatch rate and delayed somite ***,ETU treatment significantly reduced the dark velocity in the locomotion *** upregulated tendency of the mitogen-activated protein kinases(mapk)pathway(mknk1,atf4,mapkapk3)screened by transcriptome analysis implied motor neuron degeneration,which was validated by subsequent morphological observation,as axon length and branches were truncated in the 62.5μg/L ETU ***,although the rescue experiment with a p38 mapk inhibitor(SB203580)successfully ameliorated axon degeneration,it failed to reverse the locomotion *** exploration of transcriptome data revealed the varied expression of presynaptic scaffold protein-related genes(pcloa,pclob,bsna),whose downregulation might impair the neuromuscular junction(NMJ).Therefore,we reasonably suspected that ETU-induced neurobehavioral deficits might result from the combined effects of the mapk pathway and presynaptic *** this,we highlighted the necessity to take precautions and early interventions for susceptible ETU-exposed populations.

关键词： Ethylene thiourea(ETU) Behavior Neuromuscular junction mapk signaling pathway Piccolo and bassoon Danio rerio

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Eudesmane-guaiane sesquiterpenoid dimers from Aucklandia cos-tus trigger paraptosis-like cell death via ROS accumulation and mapk hyperactivation

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Chinese Journal of Natural Medicines 2024年第11期22卷 1011-1019页

作者： XIAO Longgao ZHAO Yueqin DING Xiao LIU Hui ZHU Guangyu LI Yanxi YAN Huan FANG Xin ZHAO Yuhan LIU Haiyang State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal ChemistryKunming Institute of BotanyChinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China Yunnan Characteristic Plant Extraction Laboratory Kunming 650106China

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus *** structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)***,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid ***,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 *** 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with *** studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the mapk signaling pathway.

关键词： Aucklandia costus Sesquiterpenoid heterodimers Auckcostusolides A-CParaptosis mapk signaling pathway

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Transcriptomic analysis of bisphenol AF on early growth and development of zebrafish(Danio rerio)larvae

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Environmental Science and Ecotechnology 2020年第4期4卷 1-11页

作者： Rongzhen Li Shuai Liu Wenhui Qiu Feng Yang Yi Zheng Ying Xiong Guanrong Li Chunmiao Zheng State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control School of Environmental Science and EngineeringSouthern University of Science and TechnologyShenzhen518055China Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control School of Environmental Science and EngineeringSouthern University of Science and TechnologyShenzhen518055China School of Environmental and Chemical Engineering Shanghai UniversityShanghai200444China Shenzhen Municipal Engineering Lab of Environmental IoT Technologies Southern University of Science and TechnologyShenzhen518055Guangdong ProvinceChina

Bisphenol AF(BPAF),an alternative to bisphenol A,is widely detected in aquatic *** to health concerns,the toxic effects of BPAF on organisms are drawing *** present study aims to evaluate the toxicity of BPAF,combining the results of omics techniques and *** transcriptome sequencing(RNA-seq),we obtained 391,648,512,and 545 differentially expressed genes(DEGs)in 0.1,1,10,and 100 mg/L BPAF-exposed zebrafish larvae,*** ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment revealed the early development,stimulus-response,and mapk signaling pathway were significantly affected by *** addition,five hub genes(fgf3,fgf4,map2k1,myca,and casp3b)were highlighted as the key genes in mapk signaling pathway using the protein-protein interaction ***,the RNA-seq results showed that early development and stimulus-response were the main processes affected by BPAF,which was consistent with our morphological and pathological *** hatching rate of zebrafish embryos in 1 and 10 mg/L BPAF groups was significantly inhibited,and the oxidative stress indexes,including the level of total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and lipid peroxidation(LPO),were significantly increased by the 100 mg/L BPAF ***,the activity of alkaline phosphatase(AKP)was significantly decreased in all BPAF exposure *** conclusion,exposure to BPAF at environmental relevant concentrations affected the early development and immune system of zebrafish larvae by modulating mapk signaling pathway,and our results provide solid evidence for the future studies on the toxicity of bisphenols.

关键词： Bisphenol AF Zebrafish Early development Oxidative stress mapk signaling pathway

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MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the mapk pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis

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World Journal of Gastroenterology 2023年第29期29卷 4542-4556页

作者： Xia Li Joanna J Tibenda Yi Nan Shi-Cong Huang Na Ning Guo-Qing Chen Yu-Hua Du Ya-Ting Yang Fan-Di Meng Ling Yuan College of Pharmacy Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Ningxia Chinese Medicine Reserch Center Yinchuan 750004Ningxia Hui Autonomous RegionChina Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Traditional Chinese Medicine College Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Gastric carcinoma(GC)is the third most frequent cause of cancer-related death,highlighting the pressing need for novel clinical treatment *** this regard,microRNAs(miRNAs)have emerged as a promising therapeutic *** have shown that miRNAs can regulate related signaling pathways,acting as tumor suppressors or tumor *** To explore the effect of miR-204-3p on GC *** We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction,followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC ***-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells,and the colony formation ability of GC cells was detected by the clonal formation *** effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow *** BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC ***,the study investigated the effects of miR-204-3p on various proteins related to the mapk signaling pathway,necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot *** Firstly,we found that the expression of miR-204-3p in GC was *** treated with the lentivirus overexpression vector,miR-204-3p expression significantly increased,but the lentivirus knockout vector had no significant effect on *** vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability,promoted cell apoptosis,blocked the cell cycle,and inhibited colony formation *** vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude ***,our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the mapk pa

关键词： miR-204-3p Gastric carcinoma mapk signaling pathway Apoptosis Necroptosis

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