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CypA/CD147及MMP-2在人慢性牙周炎牙龈组织中cd68^(+)细胞上表达的研究

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中国病理生理杂志 2022年第11期38卷 2055-2062页

作者：余施雷李娟杨婷黄世光杭州牙科医院浙江杭州310000 暨南大学口腔医学院广东广州510632

目的:观察亲环素A(CypA)、CD147及基质金属蛋白酶2(MMP-2)在人慢性牙周炎患者牙龈组织中cd68^(+)细胞(单核细胞/巨噬细胞)的表达情况,探讨cd68^(+)细胞中CypA、CD147及MMP-2在不同病变程度牙周炎牙龈组织中的表达及作用机制。方法:将60... 详细信息

目的:观察亲环素A(CypA)、CD147及基质金属蛋白酶2(MMP-2)在人慢性牙周炎患者牙龈组织中cd68^(+)细胞(单核细胞/巨噬细胞)的表达情况,探讨cd68^(+)细胞中CypA、CD147及MMP-2在不同病变程度牙周炎牙龈组织中的表达及作用机制。方法:将60例受试者分为4组,每组15例,分别为:健康组及慢性牙周炎(轻、中、重)组。免疫荧光双染色(DIF)后荧光显微镜下分别观察牙龈组织中cd68-CypA、cd68-CD147及cd68-MMP-2双阳性细胞表达情况并计算单位面积双阳性细胞密度。结果:(1)各组牙龈组织中cd68-CypA、cd68-CD147及cd68-MMP-2双阳性细胞密度差异显著(Pcd68-CypA双阳性细胞(r=0.959,P=0.000)、cd68-CD147双阳性细胞(r=0.948,P=0.000)及cd68-MMP-2双阳性细胞密度(r=0.945,P=0.000)与牙周炎的严重程度呈正相关;(3)各组牙龈组织中cd68-CypA与cd68-MMP-2双阳性表达正向相关(r=0.933,P=0.000);cd68-CD147与cd68-MMP-2双阳性表达水平正相关(r=0.954,P=0.000)。结论:牙龈组织中cd68-CypA、cd68-CD147及cd68-MMP2双阳性细胞密度随牙周病程加重而增多,且cd68-CypA和cd68-CD147双阳性细胞的密度与cd68-MMP-2双阳性细胞密度呈正相关。

关键词：慢性牙周炎 cd68^(+)细胞亲环素A CD147 基质金属蛋白酶2

MiR-125b-5p抑制卵巢癌细胞的迁移和侵袭:基于靶向下调CD147的表达

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南方医科大学学报 2022年第9期42卷 1389-1396页

作者：黄珍沈浩明邓红玉孙丽莎屈斌湖南省人民医院血液科湖南长沙410005 湖南省肿瘤医院2检验科湖南长沙410009 湖南省肿瘤医院输血科湖南长沙410009

目的探讨miR-125b-5p靶向调控细胞外基质金属蛋白诱导因子(CD147)表达对卵巢癌细胞生物学行为的影响及作用机制。方法应用荧光实时定量PCR技术(RT-qPCR)检测卵巢癌组织和癌细胞株中miR-125b-5p和CD147 mRNA的表达;构建过表达miR-125b-5p... 详细信息

目的探讨miR-125b-5p靶向调控细胞外基质金属蛋白诱导因子(CD147)表达对卵巢癌细胞生物学行为的影响及作用机制。方法应用荧光实时定量PCR技术(RT-qPCR)检测卵巢癌组织和癌细胞株中miR-125b-5p和CD147 mRNA的表达;构建过表达miR-125b-5p的SKOV3细胞或低表达miR-125b-5p的HO8910细胞。CCK-8实验、克隆形成实验、Transwell实验检测过表达或低表达miR-125b-5p对卵巢癌细胞的增殖、迁移和侵袭能力的影响;使用Starbase(http://***/)生信软件预测miR-125b-5p与CD147之间的潜在互补结合位点并使用双荧光素酶报告基因实验进行验证其靶向关系;体外培养SKOV3细胞,分别转染mimic NC、miR-125b-5p mimic、miR-125b-5p mimic和pcdNA3.1、miR-125b-5p mimic和pcdNA3.1-CD147,转染后分为mimic NC组、miR-125b-5p mimic组、miR-125b-5p mimic组+pcdNA3.1组、miR-125b-5p mimic+pcdNA3.1-CD147组,应用RT-qPCR和Westemblot实验检测各组中miR-125b-5p水平,CD147蛋白和mRNA水平;应用CCK-8实验、Transwell实验检测各组卵巢癌细胞的增殖、迁移和侵袭能力。结果RT-qPCR技术证实miR-125b-5p在癌组织和卵巢癌细胞株中均低表达,而CD147在癌组织和卵巢癌细胞株中均高表达(PCD147存在一个靶向调控关系;在SKOV3细胞中转染过表达质粒和对照质粒,转染成功后,过表达miR-125b-5p组中miR-125b-5p的表达升高,而CD147的mRNA和蛋白表达明显下降(PcdNA3.1-CD147,CD147的mRNA和蛋白表达明显升高(PCD147,卵巢癌细胞的增殖、侵袭和迁移的能力得到增强。结论miR-125b-5p通过负向调控CD147的表达,从而抑制卵巢癌细胞的迁移与侵袭。

关键词：卵巢癌 miR-125b-5p CD147 迁移侵袭

附睾4-5段CD147缺失对精子成熟的作用研究

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中华生殖与避孕杂志 2022年第10期42卷 995-1002页

作者：田家玮戴鹏远陈浩南通大学医学院生殖医学研究院南通226001

目的研究小鼠附睾上皮表达的CD147对精子成熟的影响。方法利用小鼠附睾4-5段主细胞特异表达的Lcn5-Cre小鼠和CD147^(flox/flox)繁育,获得24只CD147在附睾4-5段特异敲除的小鼠(CD147 cKO-Lcn5)和21只CD147^(flox/flox)对照小鼠。通过计... 详细信息

目的研究小鼠附睾上皮表达的CD147对精子成熟的影响。方法利用小鼠附睾4-5段主细胞特异表达的Lcn5-Cre小鼠和CD147^(flox/flox)繁育,获得24只CD147在附睾4-5段特异敲除的小鼠(CD147 cKO-Lcn5)和21只CD147^(flox/flox)对照小鼠。通过计算机辅助精子活力检测(computer-aided sperm analysis,CASA)、A23187诱导精子的顶体反应以及体外受精(invitro fertilization,IVF)等方法评估CD147对小鼠精子功能的影响。结果小鼠附睾头部4-5段敲除CD147后,精子活力和顶体反应的差异均无统计学意义(均P>0.05)。IVF实验结果显示,CD147 cKO-Lcn5小鼠2-细胞率(74.03%±2.93%)相较于CD147^(flox/flox)小鼠(90.59%±2.39%)显著降低(P=0.012)。结论附睾头部4-5段敲除CD147后对精子活力和顶体反应无显著影响,IVF后2-细胞率显著被抑制。

关键词：精子成熟受精,体外 CD147 附睾4-5区段

CD147 deficiency in T cells prevents thymic involution by inhibiting the EMT process in TECs in the presence of TGFβ

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Cellular & Molecular Immunology 2021年第1期18卷 171-181页

作者： Ruo Chen Ke Wang Zhuan Feng Ming-Yang Zhang Jiao Wu Jie-Jie Geng Zhi-Nan Chen Department of Cell Biology College of Life Science and TechnologyJinan UniversityGuangdongChina National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityShaanxiChina

Thymic involution during aging is a major cause of decreased T-cell production and reduced immunity.Here,we show that the loss of CD147 on T cells prevents thymic senescence,resulting in slowed shrinkage of the thymus with age and increased production of naive T cells.This phenotype is the result of slowing of the epithelial-mesenchymal transition(EMT)process in thymic epithelial cells(TECs),which eventually leads to reduced adipocyte accumulation.In an in vitro coculture system,we found that TGFβ is an important factor in the EMT process in TECs and that it can reduce the expression of E-cadherin through p-5mad2/FoxC2 signaling.Moreover,CD147 on T cells can accelerate the decline in E-cadherin expression by interacting with Annexin A2 on TECs.In the presence of TGFβ,Annexin A2 and E-cadherin colocalize on TECs.However,CD147 on T cells competitively binds to Annexin A2 on TECs,leading to the isolation of E-cadherin.Then,the isolated E-cadherin is easily phosphorylated by phosphorylated Src kinase,the phosphorylation of which was induced by TGFβ,and finally,p-E-cadherin is degraded.Thus,in the thymus,the interaction between T ceils and TECs contributes to thymic involution with age.In this study,we illuminate the mechanism underlying the triggering of the EMT process in TECs and show that inhibiting TGFβ and/or CD147 may serve as a strategy to hinder age-related thymic involution.

关键词： CD147 TGFβ thymic involution EMT

沉默CD147对前列腺癌LNCaP细胞糖酵解的影响

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吉林大学学报（医学版） 2023年第3期49卷 634-639页

作者：张斯琦孙美琪李泽颢刘丹丹胡城方芳王国庆北华大学医学技术学院临床生化检验教研室吉林吉林132013 吉林医药学院检验学院免疫学技术教研室吉林吉林132013

目的:探讨CD147对前列腺癌(PCa)LNCaP细胞糖酵解的影响,为PCa临床诊断和治疗提供新的分子标志物和靶点。方法:采用慢病毒感染系统建立沉默CD147的细胞作为LNCaP/shCD147组,同时设立阴性对照组(LNCaP/scramble组)。采用实时荧光定量PCR(R... 详细信息

目的:探讨CD147对前列腺癌(PCa)LNCaP细胞糖酵解的影响,为PCa临床诊断和治疗提供新的分子标志物和靶点。方法:采用慢病毒感染系统建立沉默CD147的细胞作为LNCaP/shCD147组,同时设立阴性对照组(LNCaP/scramble组)。采用实时荧光定量PCR(RT-qPCR)法检测2组LNCaP细胞中CD147 mRNA表达水平,试剂盒检测2组LNCaP细胞中乳酸(LA)、丙酮酸(PA)和腺嘌呤核苷三磷酸(ATP)浓度及2组LNCaP细胞中丙酮酸激酶(PK)、6-磷酸果糖激酶1(PFK1)和己糖激酶(HK)酶活性,Western blotting法检测2组LNCaP细胞中CD147、HK2、肌肉磷酸果糖激酶(PFKM)和丙酮酸激酶M2(PKM2)蛋白表达水平。结果:与LNCaP/scramble组比较,LNCaP/shCD147组细胞中CD147 mRNA和蛋白表达水平明显降低(PCD147的PCa LNCaP细胞模型。与LNCaP/scramble组比较,LNCaP/shCD147组细胞中LA、PA和ATP浓度明显降低(PCD147组细胞中PK、PFK1和HK酶活性明显降低(PCD147组细胞中HK2蛋白表达水平明显降低(PCD147通过调节糖酵解代谢产物、限速酶活性和相关蛋白表达水平抑制LNCaP细胞糖酵解过程。

关键词： CD147 糖酵解前列腺肿瘤 LNCaP细胞己糖激酶2

HIF-1α可能通过增加CD147和GLUT1的表达促进寻常型银屑病的糖酵解过程

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中南大学学报（医学版） 2021年第4期46卷 333-344页

作者：唐雯龙婷婷李芳芳彭聪赵爽陈翔粟娟中南大学湘雅医院老年医学科长沙410008 中南大学湘雅医院皮肤肿瘤与银屑病湖南省重点实验室长沙410008 中南大学湘雅医院皮肤科长沙410008

目的:分析缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)、白细胞分化抗原147(CD147)及葡萄糖转运蛋白1(glucose transporter 1,GLUT1)在寻常型银屑病皮损和正常人表皮中的分布与表达,并探索这些蛋白质之间的关联及其在缺氧... 详细信息

目的:分析缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)、白细胞分化抗原147(CD147)及葡萄糖转运蛋白1(glucose transporter 1,GLUT1)在寻常型银屑病皮损和正常人表皮中的分布与表达,并探索这些蛋白质之间的关联及其在缺氧的人永生化表皮细胞(HaCaT细胞)中的作用。方法:采用免疫组织化学法分析48例寻常型银屑病患者及33例正常人皮肤活检组织中HIF-1α、CD147和GLUT1蛋白质的表达;在HaCaT细胞系中运用氯化钴诱导缺氧、RNA干扰和转染技术后,通过实时RT-PCR和蛋白质印迹法探索蛋白质间的关联;通过检测ATP和乳酸浓度反映皮肤组织和HaCaT细胞的糖酵解能力。结果:寻常型银屑病皮损中HIF-1α,CD147,GLUT1的表达增加及糖酵解能力增强;在诱导HaCaT细胞缺氧的过程中,HIF-1α使CD147和GLUT1的表达增加,同时乳酸浓度升高及ATP浓度降低,而CD147和GLUT1之间也存在直接或间接的结合。结论:糖酵解能力在寻常型银屑病皮损中增强,提示与其有关的HIF-1α,CD147,GLUT1可作为银屑病潜在的治疗靶点。

关键词：缺氧诱导因子1α 糖酵解银屑病 CD147 葡萄糖转运蛋白1

RNA干扰抑制CD147表达对宫颈癌细胞增殖、转移和侵袭能力的影响

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中国免疫学杂志 2023年第2期39卷 349-353,358页

作者：曹勋荣吕桂雪魏雯雯济南市第二妇幼保健院妇产科济南271100

目的:探讨RNA干扰(RNAi)对宫颈癌组织CD147表达及对宫颈癌HeLa细胞增殖、迁移和侵袭的影响。方法:选取2016年2月至2019年2月济南市第二妇幼保健院病理组织室110份宫颈组织,包括20例正常宫颈上皮组织和90例宫颈癌组织(30例原位宫颈癌组织... 详细信息

目的:探讨RNA干扰(RNAi)对宫颈癌组织CD147表达及对宫颈癌HeLa细胞增殖、迁移和侵袭的影响。方法:选取2016年2月至2019年2月济南市第二妇幼保健院病理组织室110份宫颈组织,包括20例正常宫颈上皮组织和90例宫颈癌组织(30例原位宫颈癌组织和60例鳞状宫颈癌组织),免疫组化检测CD147表达。分析CD147表达与宫颈癌患者临床病理参数的相关性。以GFP-shRNA-CD147-NC和GFP-shRNA-CD147分别转染对照组和实验组细胞,另取空白细胞作为正常组。EdU标记实验检测细胞增殖;Transwell检测细胞迁移和侵袭;裸鼠成瘤模型检测细胞体内生长与转移能力;Western blot检测细胞单羧酸转运蛋白1(MCT1)、CD147蛋白表达。结果:与正常宫颈组织相比,原位宫颈癌组织中CD147阳性表达比例明显升高,与原位宫颈癌组织相比,鳞状宫颈癌组织中CD147阳性表达比例明显升高(PCD147表达与宫颈癌患者肿瘤大小、浸润深度、淋巴转移关系密切(均PCD147蛋白表达明显下调(均PCD147表达升高,抑制CD147表达可明显抑制肿瘤细胞体内外增殖、侵袭和转移。

关键词： RNA干扰 CD147 宫颈癌增殖迁移侵袭

Synthesis and Evaluation of a Novel Small-molecule Compound as an Anticancer Inhibitor of CD147

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Biomedical and Environmental Sciences 2019年第9期32卷 673-686页

作者： FU Zhi Guang WANG Yan WANG Shuang SHAO Dan TIAN Li LI Yun Xia JIANG Jian Li CHEN Zhi Nan WEN Ning Department of Stomatology Chinese PLA General HospitalBeijing 100850China Cell Engineering Research Center&Department of Cell Biology State Key Laboratory of Cancer BiologyNational Key Discipline of Cell BiologyFourth Military Medical UniversityXi'an 710032ShaanxiChina Department of Internal Neurology 309 Hospital of PLABeijing 100091China Department of Stomatology Huangdao District Central HospitalQingdao266000ShandongChina Department of Anesthesiology&Perioperative Medicine Xijing HospitalFourth Military Medical UniversityXi'an 710032ShaanxiChina Outpatient Department Special Police College of the Chinese Armed Police ForceBeijing 100621China

Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-cd44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.

关键词： Antigens CD147 Antineoplastic agents Apoptosis

CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

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Signal Transduction and Targeted Therapy 2021年第1期6卷 95-104页

作者： Ke Wang Wei Chen Zheng Zhang Yongqiang Deng Jian-Qi Lian Peng Du Ding Wei Yang Zhang Xiu-Xuan Sun Li Gong Xu Yang Lei He Lei Zhang Zhiwei Yang Jie-Jie Geng Ruo Chen Hai Zhang Bin Wang Yu-Meng Zhu Gang Nan Jian-Li Jiang Ling Li Jiao Wu Peng Lin Wan Huang Liangzhi Xie Zhao-Hui Zheng Kui Zhang Jin-Lin Miao Hong-Yong Cui Min Huang Jun Zhang Ling Fu Xiang-Min Yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe Wang Chun-Fu Wang Yacheng Lu Ying-Ying Liu Qing-Yi Wang Huijie Bian Ping ZhuZhi-Nan Chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Biotechnology Beijing 100071China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Tangdu Hospital Fourth Military Medical UniversityXi’an 710038China MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter Xi’an Jiaotong UniversityXi’an 710049China Sino Biological Inc. Beijing 100176China Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi’an 710032China School of Basic Medicine Fourth Military Medical UniversityXi’an 710032China

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.

关键词： ACE2 CD147 intestine