检索结果-南通市图书馆

维普期刊数据库

Transcriptome-based analysis of key signaling pathways affecting the formation of primordial germ cell in chickens

在线全文

学校读者我要写书评

暂无评论

Journal of Integrative Agriculture 2024年第5期23卷 1644-1657页

作者： Ying Ding Qiong Zhi Qisheng Zuo Kai Jin Wei Han Bichun Li Key Laboratory of Animal Genetics Breeding and Molecular Design of Jiangsu ProvinceCollege of Animal Science and TechnologyYangzhou UniversityYangzhou 225009China Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China Yangzhou UniversityYangzhou225009China Poultry Research Institute Chinese Academy of Agricultural Sciences/Jiangsu Institute of Poultry ScienceYangzhou 225009China

Bone morphogenetic protein 4(bmp4)can induce the formation of chicken primordial germ cells(PGCs)in vitro;however,its regulatory mechanism in poultry remains unknown.This study aimed to use RNA-seq to analyze PGCs in chicken embryos and iPGCs induced by bmp4 in vitro,clarify the internal regulatory factors of PGCs,analyze the mechanism of the formation of PGCs,and lay a theoretical foundation for the further optimization of PGCs induction systems.Embryonic stem cells(ESCs),PGCs and iPGCs induced by bmp4 in vitro were collected.The transcriptional maps of the three cell types were studied using RNA-seq.The results showed 6,142 genes differentially expressed between PGCs and iPGCs,of which 2,728 were upregulated in iPGCs and 3,414 were downregulated in iPGCs.Compared to that in ESCs,bmp4 was significantly upregulated in PGCs and iPGCs.KEGG results showed that both the TGF-βand Wnt signaling pathways were activated during the formation of PGCs in vitro and in vivo,and the activation was more significant during iPGCs induced by bmp4.The expression of Nodal,an inhibitory factor of TGF-βsignaling,was significantly decreased in PGCs and iPGCs,but was not expressed in iPGCs,which further supports our conclusion.Additionally,the Lysosome and PI3K-AKT signaling pathways were significantly enriched in PGCs and iPGCs,respectively.Further,transmission electron microscopy(TEM)results showed that the number of autolysosomes was significantly higher after the addition of bmp4,which is consistent with the KEGG results.Furthermore,the number of PGCs was significantly reduced after ATG14 was interfered in vivo and in vitro.In conclusion,this study screened out the key signaling pathways during the formation of PGCs,aiming to provide help for enriching the mechanism network regulating PGCs formation in chicken and laying a theoretical foundation for further improving the efficiency of inducing PGCs in vitro.

关键词： RNA-seq bmp4 PGCs ATG14 chicken

维普期刊数据库

FGF20抑制bmp4改善异丙肾上腺素诱导的心肌细胞肥大的作用研究

在线全文

学校读者我要写书评

暂无评论

中国细胞生物学学报 2024年第7期 1335-1346页

作者：梅淋王旭陈慧楠周旋陈云杰厦门医学院药学系温州医科大学药学院宁波大学附属第一医院药学部

成纤维细胞生长因子20(fibroblast growth factor 20, FGF20)在心肌肥大中具有保护作用,但其作用机制尚未明确。因此,该研究旨在探究FGF20改善心肌细胞肥大的分子作用机制。该研究使用10μmol/L异丙肾上腺素(isoproterenol, ISO)刺激原... 详细信息

成纤维细胞生长因子20(fibroblast growth factor 20, FGF20)在心肌肥大中具有保护作用,但其作用机制尚未明确。因此,该研究旨在探究FGF20改善心肌细胞肥大的分子作用机制。该研究使用10μmol/L异丙肾上腺素(isoproterenol, ISO)刺激原代心肌细胞NRCMs 48 h,构建心肌细胞肥大模型,并同时对NRCMs分别给予100 ng/mL重组蛋白FGF20以及50 ng/mL重组蛋白骨形态发生蛋白4 (bone morphogenetic protein 4, bmp4)共处理48 h,并借助转录组测序分析FGF20处理前后的差异表达基因(differential expression genes, DEGs),再对其进行GO和KEGG富集分析以及PPI网络构建。使用机器学习算法LASSO和Random Forest筛选得出核心差异基因(Core-DEGs),并对其进行ROC分析。最后,使用蛋白质免疫印迹以及RT-qPCR验证核心差异基因的表达, TUNEL染色实验检测心肌细胞凋亡情况。结果表明,FGF20可抑制ISO诱导的心肌肥大指标ANP、BNP表达上调,证实FGF20具有心肌细胞肥大保护作用。转录组测序分析发现,与ISO组相比, FGF20处理后共鉴定出42个差异表达基因。GO和KEGG富集分析结果表明,差异表达基因主要富集在多个免疫调控以及凋亡信号通路。2种机器学习算法联合筛选后发现bmp4为Core-DEGs,且其AUC为1。实验结果表明, FGF20可抑制ISO诱导的bmp4表达上调以及心肌细胞凋亡;而bmp4激活后FGF20心肌细胞肥大保护作用被明显削弱,并伴随ANP、BNP蛋白水平上调以及心肌细胞凋亡增多。总之,FGF20通过抑制bmp4缓解心肌细胞凋亡进而改善心肌细胞肥大。

关键词： FGF20 心肌细胞肥大 bmp4 凋亡转录组机器学习算法

bmp4通过调控FOXO1影响RSA患者子宫内膜蜕膜化

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

医学研究杂志 2024年

作者：黄燕洁代芳芳陈丽萍程艳香武汉大学人民医院妇产科

目的探讨骨形态发生蛋白4（Bonemorphogeneticprotein4，bmp4）在复发性流产（Recurrentspontaneousabortion，RSA)患者的人子宫内膜基质细胞（Humanendometrialstromalcells，hESCs）中的表达及对叉头盒转录因子1（Forkheadtranscriptionfactors，FOXO1）的调控。方法收集武汉大学人民医院RSA患者和健康对照(Healthycontrol，HC)患者的蜕膜组织，通过免疫组化和qRT-PCR分析蜕膜中bmp4的表达。利用hESC进行体外细胞实验，通过转染慢病毒敲低bmp4，建立RSA细胞模型，蜕膜化后，通过CCK-8实验、倒置显微镜和Western Blot检测各组细胞的增殖、形态及蜕膜化标志基因的表达。验证bmp4敲低是否影响FOXO1表达，并使用FOXO1抑制剂（AS1842856）进行回复实验，CCK-8实验、倒置显微镜和Western Blot分析FOXO1与bmp4的上下游关系。动物试验中，对孕鼠腹腔注射LPS诱导流产，检测bmp4在小鼠蜕膜中的表达，探究bmp4与小鼠流产的关系。结果与HC组相比，RSA患者的蜕膜中bmp4表达量明显降低，敲低bmp4后，细胞蜕膜化异常，表现为增殖速度上升，细胞形态转变不明显，且蜕膜化标志基因表达下调。FOXO1为bmp4的下游调控分子，敲低bmp4抑制FOXO1表达，且bmp4可通过FOXO1调控蜕膜化，动物模型中，流产孕鼠蜕膜中bmp4表达量及胎盘重量显著降低。结论 bmp4在RSA患者和流产小鼠蜕膜中的表达下调，细胞实验中，bmp4可通过调控FOXO1的表达促进蜕膜化，bmp4异常低表达可能为RSA患者蜕膜化缺陷的原因之一。

关键词：复发性流产 bmp4 FOXO1 蜕膜化缺陷

bmp4 preserves the developmental potential of mESCs through Ube2s-and Chmp4b-mediated chromosomal stability safeguarding

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Protein & Cell 2022年第8期13卷 580-601页

作者： Mingzhu Wang Kun Zhao Meng Liu Mengting Wang Zhibin Qiao Shanru Yi Yonghua Jiang Xiaochen Kou Yanhong Zhao Jiqing Yin Tianming Li Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalTongi UniversityShanghai 200065China Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200123China Guangxi Key Laboratory of Genomic and Personalized Medicine Nanning 530021China

Chemically defined medium is widely used for culturing mouse embryonic stem cells(mESCs),in which N2B27 works as a substitution for serum,and GSK3βand MEK inhibitors(2i)help to promote ground-state pluripo-tency.However,recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs.Here,we demon-strated the deficient bone morphogenetic protein(bmp)signal in the chemically defined condition is one of the main causes for the impaired pluripotency.Mechanisti-cally,activating the bmp signal pathway by bmp4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream tar-gets Ube2s and Chmp4b.More importantly,bmp4 pro-motes a distinct in vivo developmental potential and a long-term pluripotency preservation.Besides,the pluripotent improvements driven by bmp4 are superior to those by attenuating MEK suppression.Taken together,our study shows appropriate activation of bmp signal is essential for regulating functional pluripotency and reveals that bmp4 should be applied in the serum-free culture system.

关键词： bmp4 pluripotency chromosomal integrity developmental potential serum-lree

Glioma stem cells and neural stem cells respond differently to bmp4 signaling

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cell Regeneration 2022年第1期11卷 374-388页

作者： Xin-Xin Han Chunhui Cai Li-Ming Yu Min Wang Wenhan Yang Dai-Yu Hu Jie Ren Lu-Ying Zhu Jia-Jia Deng Qing-Qing Chen Hua He Zhengliang Gao Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghai 200001China Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Tongji University School of MedicineShanghai 200072China Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)School of MedicineShanghai UniversityNantongChina School of Medicine Jiax-ing UniversityJiaxingChina Department of Neurosurgery Changzheng HospitalSecond Military Medical UniversityShanghaiChina Department of Neurosurgery Third Affiliated Hospital of Second Military Medical UniversityShanghaiChina

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates,resistance to combined therapy,and dismal prognosis.Glioma stem cells(GSCs)are likely responsible for tumor progression,resistance to therapy,recurrence,and poor prognosis owing to their high self-renewal and tumorigenic potential.As a family member of bmp signaling,bone morphogenetic protein4(bmp4)has been reported to induce the differentiation of GSCs and neural stem cells(NSCs).However,the molecular mechanisms underlying the bmp4-mediated effects in these two cell types are unclear.In this study,we treated hGSCs and hNSCs with bmp4 and com-pared the phenotypic and transcriptional changes between these two cell types.Phenotypically,we found that the growth of hGSCs was greatly inhibited by bmp4,but the same treatment only increased the cell size of hNSCs.While the RNA sequencing results showed that bmp4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs,the profiles of differentially expressed genes were distinct between the two groups.A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture.Our results suggested that hGSCs and hNSCs responded differently to bmp4 stimulation.Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with bmp4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

关键词： Glioma stem cells bmp4 Neural stem cells Cell differentiation Cell proliferation

bmp4 facilitates beige fat biogenesis via regulating adipose tissue macrophages

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2019年第1期11卷 14-25页

作者： Shu-Wen Qian Meng-Yuan Wu Yi-Na Wang Ya-Xin Zhao Ying Zou Jia-Bao Pan Yan Tang Yang Liu Liang Guo Qi-Qun Tang Key Laboratory of Metabolism and Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologyFudan University Shanghai Medical CollegeShanghai 200032China

Thermogenic beige fat improves metabolism and prevents obesity.Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis,whereas the activation of Ml macrophages,which play a major role in inflammation,impedes beige adipogenesis.Thus,the identification of factors that regulate adipose tissue macrophages(ATMs)will help clarify the mechanism involved in beiging.Here,we found that one of the secreted proteins in adipose tissue,namely,bmp4,alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting Ml macrophages.Mechanistically,the bmp4-stimutated p38/MAPK/STAT6/PI3K-AKT signalling pathway is involved.Meanwhile,bmp4 improved the potency of M2 macrophages to induce beige fat biogenesis.Considering that the overexpression of bmp4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity,these findings provide evidence that bmp4 acts as an activator of beige fat by targeting immuno-metabolic pathways.

关键词： bmp4 fat browning adipose tissue macrophages

Rat adipose-derived stromal cells expressing bmp4 induce ectopic bone formation in vitro and in vivo

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2006年第12期27卷 1608-1615页

作者： Lin LIN~2 Xin FU~2 Xin ZHANG~2 Lian-xu CHEN~2 Ji-ying ZHANG~2 Chang-long YU~(2,4)Kang-tao MA~3 Chun-yan ZHOU~(3,4)2 Institute of Sports Medicine,Peking University Third Hospital,Beijing 100083,China 3 Department of Biochemistry and Molecular Biology,Peking University School of Basic Medical Science,Beijing 100083,China Institute of Sports Medicine Peking University Third Hospital Beijing China Department of Biochemistry and Molecular Biology Peking University School of Basic Medical Science Beijing China

Aim:Bone morphogenetic protein 4(bmp4)is one of the main local contributingfactors in callus formation in the early phase of fracture healing.Adipose-derivedstromal cells(ADSC)are multipotent cells.The present study was conducted toinvestigate the osteogenic potential of ADSC when exposed to adenovirus con-taining bmp4 cDNA(Ad-bmp4).Methods:ADSC were harvested from Sprague-Dawley rats.After exposure to Ad-bmp4,ADSC were assessed by alkaline phos-phatase activity(ALP)assay,RT-PCR and yon Kossa staining.bmp4 expressionwas assessed by RT-PCR,immunofluorescence and Western blot analysis,ADSCtransduced with Ad-bmp4 were directly injected into the hind limb muscles ofathyrnic mice.ADSC Ad-EGFP(enhanced green fluorescence protein)served ascontrols.All animals were examined by X-ray film and histological analysis.Results:The expression of bmp4 was confirmed at both mRNA and protein levels.The expression of the osteoblastic gene,ALP activity and yon Kossa stainingconfirmed that ADSC transduced with Ad-bmp4 underwent rapid and markedosteoblast differentiation,whereas ADSC transduced with Ad-EGFP and cells leftalone displayed no osteogenic differentiation.X-ray and histological examinationconfirmed new bone formation in athymic mice transplanted with ADSC trans-duced with Ad-bmp4.Conclusion:Our data demonstrated successful osteo-genic differentiation of ADSC transduced with Ad-bmp4 in vitro and in vivo.ADSC may be an ideal source of mesenchyme lineage stem cells for gene therapyand tissue engineering.

关键词： adipose-derived stromal cells bmp4 gene therapy bone formation

Bone morphogenetic protein 4 (bmp4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Genes & Diseases 2021年第4期8卷 531-544页

作者： Liqin An Qiong Shi Ying Zhu Hao Wang Qi Peng Jinghong Wu Yu Cheng Wei Zhang Yanyu Yi Zihao Bao Hui Zhang Yetao Luo Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine Department of Clinical BiochemistrySchool of Laboratory MedicineChongqing Medical UniversityChongqing400016PR China Department of Clinical Laboratory The Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China Clinical Epidemiology and Biostatistics Department Department of Pediatric Research InstituteChildren’s Hospital of Chongqing Medical UniversityChongqing400014PR China

Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(bmps)may play important roles in regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that bmp4 signif-icantly inhibits hepatic steatosis and lowers serum triglycerides,playing a protective role against the progression of non-alcoholic fatty liver disease(NAFLD).However,the direct impact of bmp4 on hepatic glucose metabolism is poorly understood.Here,we investigated the regulatory roles of bmp4 in hepatic glucose metabolism.Through a comprehensive analysis of the 14 types of bmps,we found that bmp4 was one of the most potent bmps in promoting hepatic glycogen accumulation,reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism.Mechanistically,we demonstrated that bmp4 reduced the hepatic glucose lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.Collectively,our findings strongly suggest that bmp4 may play an essential role in regulating hepatic glucose metabolism.This knowledge should aid us to understand the molecular pathogenesis of NAFLD,and may lead to the development of novel therapeutics by exploiting the inhibitory effects of bmps on hepatic glucose and lipid metabolism.

关键词： bmp4 Glucose metabolism Glycogen accumulation mTORC2 signaling Non-alcoholic fatty liver disease(NAFLD)

Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

分子细胞生物学报:英文版 2015年第5期7卷 455-465页

作者： Lingyu Li Lu Song Chang Liu Jun Chen Guangdun Peng Ran Wang Pingyu Liu Ke Tang Janet Rossant Naihe Jing State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Institute of Life Science Nanchang UniversityNanchang 330031JiangxiChina Program in Developmental and Stem Cell Biology Hospital for Sick Children Research InstituteTorontoON M5G 1X8Canada Department of Developmental Biology Stanford University School of MedicineStanfordCA 94305USA

The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development.Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation.Here,we demonstrate that through brief inhibition of Nodal signaling in vitro,mouse embryonic stem cell(ESC)-derived epiblast stem cells(ESD-EpiSCs)could be committed to transient ectodermal progenitor populations,which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of bmp4,respectively.Mechanistic studies reveal that bmp4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells.Furthermore,FGF–Erk signaling may also be alleviated during the generation of ectoderm-like cells.Thus,our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs,which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.

关键词： EpiSCs ectoderm bmp4 Nodal FGF