更新于：2024-05-01

MSR1

macrophage scavenger receptor 1

更新于：2024-05-01

基本信息

别名

CD204、Macrophage acetylated LDL receptor I and II、macrophage scavenger receptor 1

+ [8]

简介

Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL) (PubMed:2251254). Isoform III does not internalize acetylated LDL (PubMed:9548586).

关联

100 项与 MSR1 相关的临床结果

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100 项与 MSR1 相关的转化医学

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0 项与 MSR1 相关的专利（医药）

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1,423

项与 MSR1 相关的文献（医药）

2024-02-13·Neurology

Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke.

Article

作者: Chad M Aldridge ; Robynne Braun ; Keith Lohse ; Adam de Havenon ; John W Cole ; Steven C Cramer ; Arne G Lindgren ; Keith L Keene ; Fang-Chi Hsu ; Bradford B Worrall

BACKGROUND AND OBJECTIVES:

Stroke genetic research has made substantial progress in the past decade. Its recovery application, however, remains behind, in part due to its reliance on the modified Rankin Scale (mRS) score as a measure of poststroke outcome. The mRS does not map well to biological processes because numerous psychosocial factors drive much of what the mRS captures. Second, the mRS contains multiple disparate biological events into a single measure further limiting its use for biological discovery. This led us to investigate the effect of distinct stroke recovery phenotypes on genetic variation associations with Genome-Wide Association Studies (GWASs) by repurposing the NIH Stroke Scale (NIHSS) and its subscores.

METHODS:

In the Vitamin Intervention for Stroke Prevention cohort, we estimated changes in cognition, motor, and global impairments over 2 years using specific measures. We included genotyped participants with a total NIHSS score greater than zero at randomization and excluded those with recurrent stroke during the trial. A GWAS linear mixed-effects model predicted score changes, with participant as a random effect, and included initial score, age, sex, treatment group, and the first 5 ancestry principal components.

RESULTS:

In total, 1,270 participants (64% male) were included with a median NIHSS score of 2 (interquartile range [IQR] 1-3) and median age 68 (IQR 59-75) years. At randomization, 20% had cognitive deficits (NIHSS Cog-4 score >0) and 70% had ≥1 motor deficits (impairment score >1). At 2 years, these percentages improved to 7.2% with cognitive deficits and 30% with motor deficits. GWAS identified novel suggestive gene-impairment associations (p < 5e^-6) for cognition (CAMK2D, EVX2, LINC0143, PTPRM, SGMS1, and SMAD2), motor (ACBD6, KDM4B, MARK4, PTPRS, ROBO1, and ROBO2), and global (MSR1 and ROBO2) impairments.

DISCUSSION:

Defining domain-specific stroke recovery phenotypes and using longitudinal clinical trial designs can help detect novel genes associated with chronic recovery. These data support the use of granular endpoints to identify genetic associations related to stroke recovery.

2024-02-10·Endocrinology

Effects of the cortisol milieu on tumor-infiltrating immune cells (TIICs) in corticotroph tumors.

Article

作者: Maki Kanzawa ; Hiroki Shichi ; Keitaro Kanie ; Masaaki Yamamoto ; Naoki Yamamoto ; Yasutaka Tsujimoto ; Hironori Bando ; Genzo Iguchi ; Shigehisa Kitano ; Naoko Inoshita ; Shozo Yamada ; Wataru Ogawa ; Tomoo Itoh ; Hidenori Fukuoka

BACKGROUND:

Corticotrophs are susceptible to lymphocyte cytotoxicity, as seen in hypophysitis, suggesting that an immunological approach may be a potential strategy for corticotroph-derived tumors.

OBJECTIVES:

We aimed clarify whether corticotroph tumors that induce hypercortisolemia (ACTHomas) could be targets for immunotherapy.

METHODS:

Tumor-infiltrating immune cells were immunohistochemically analyzed. ACTHomas (Naïve: ACTHomas without preoperative treatment) were compared with other pituitary tumors, and further divided into three different cortisol-exposed milieus: Naïve, Met (ACTHomas with preoperative metyrapone), and SCA (silent corticotroph adenomas). A three-dimensional cell culture of resected tumors was used to analyze the effects of immune checkpoint inhibitors.

RESULTS:

The number of tumor-infiltrating lymphocytes (TILs) was low in ACTHomas. Among these, the number of CD8+ cells was lower in ACTHomas than in both somatotroph) and gonadotroph tumors (P < 0.01 and P < 0.01, respectively). Then we compared the differences in TILs among Naïve, Met, and SCA. The number of CD4+ cells, but not CD8+ cells, was higher in both Met and SCA than in Naïve. Next, we investigated tumor-associated macrophages, which could negatively affect T cell infiltration. The numbers of CD163+ and CD204+ cells were positively associated with cortisol levels. Moreover, tumor size was positively correlated with the number of CD204+ cells.

CONCLUSIONS:

We found the possibility that ACTHomas were immunologically cold in a cortisol-independent manner. In contrast, the tumor infiltration of CD4+ cells and M2-macrophages were associated with the cortisol milieu. Future studies are needed to validate these results and develop effective immunotherapy while considering the cortisol milieu.

2024-02-07·Cardiovascular toxicology

Downregulation of LILRB4 Promotes Human Aortic Smooth Muscle Cell Contractile Phenotypic Switch and Apoptosis in Aortic Dissection.

Article

作者: Jianxian Xiong ; Linyuan Wang ; Xin Xiong ; Yongzhi Deng

Aortic dissection (AD) is a severe vascular disease with high rates of mortality and morbidity. However, the underlying molecular mechanisms of AD remain unclear. Differentially expressed genes (DEGs) were screened by bioinformatics methods. Alterations of histopathology and inflammatory factor levels in β-aminopropionitrile (BAPN)-induced AD mouse model were evaluated through Hematoxylin-Eosin (HE) staining and Enzyme-linked immunosorbent assay (ELISA), respectively. Reverse transcription quantitative real-time polymerase chain reaction was performed to detect DEGs expression. Furthermore, the role of LILRB4 in AD was investigated through Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry. Western blotting was employed to assess the phenotypic switch and extracellular matrix (ECM)-associated protein expressions in platelet-derived growth factor-BB (PDGF-BB)-stimulated in vitro model of AD. In the AD mouse model, distinct dissection formation was observed. TNF-α, IL-1β, IL-8, and IL-6 levels were higher in the AD mouse model than in the controls. Six hub genes were identified, including LILRB4, TIMP1, CCR5, CCL7, MSR1, and CLEC4D, all of which were highly expressed. Further exploration revealed that LILRB4 knockdown inhibited the cell vitality and migration of PDGF-BB-induced HASMCs while promoting apoptosis and G0/G1 phase ratio. More importantly, LILRB4 knockdown promoted the protein expression of α-SMA and SM22α, while decreasing the expression of Co1, MMP2, and CTGF, which suggested that LILRB4 silencing promoted contractile phenotypic transition and ECM stability. LILRB4 knockdown inhibits the progression of AD. Our study provides a new potential target for the clinical treatment of AD.

项与 MSR1 相关的新闻（医药）

2023-12-01

·奇点网

EHJ：重磅！中国药科大学团队首次发现，维生素B1补充剂焦磷酸硫胺素或可预防/治疗动脉粥样硬化丨科学大发现

*仅供医学专业人士阅读参考动脉粥样硬化（AS）是心血管疾病的罪魁祸首，它是冠状动脉疾病、外周动脉疾病和脑血管疾病最常见的基础病理，斑块在血管中的慢性积聚最终导致明显的狭窄，从而限制血液流动并导致严重的组织缺氧和炎症。我国动脉粥样硬化的发病率逐年上升，已成为中老年人最常见的疾病之一[1]。一直以来，动脉粥样硬化都被认为是一种不可逆的疾病，不过前几天，一项新研究发现，其实中年人的动脉粥样硬化斑块是有可能完全消退的。当然，我们不能干等着斑块自己消失，主动进攻才是最好的防守。近日，中国药科大学胡庆华教授团队在《欧洲心脏病学》（EHJ）杂志发表了一项重要研究成果[2]，研究者首次发现，在动脉粥样硬化早期阶段的巨噬细胞泡沫化中，嘌呤受体P2Y6R具有重要作用。更重要的是，他们发现临床常用的维生素B1补充剂焦磷酸硫胺素（TPP）具有优异的P2Y6R抑制活性，超生理剂量TPP可有效减少小鼠动脉粥样硬化，为动脉粥样硬化的治疗和预防提供了新策略。研究的第一作者为中国药科大学李叶红、周梦泽，苏州大学李环球，南京农业大学戴琛。论文首页截图巨噬细胞在动脉粥样硬化的起始和发展阶段具有重要作用，是动脉粥样硬化斑块的重要组成部分。动脉粥样硬化的病变标志，就是巨噬细胞通过清道夫受体摄取氧化的低密度脂蛋白（ox-LDL）形成的泡沫细胞，这些吸饱了胆固醇的泡沫细胞加速了动脉粥样硬化的进展。在整个心血管系统中，嘌呤受体广泛表达，对心脏功能、血管张力、血管生成和炎症调节等生理功能有重要作用。因此，研究者们猜测，嘌呤受体或许能够成为干预动脉粥样硬化的重要切入口。通过分析现有数据库和临床斑块样本，研究者发现，与健康人群相比，动脉粥样硬化患者斑块和外周血中，嘌呤受体家族成员P2Y6R高表达。对斑块中15个细胞亚群进一步分析发现，升高的P2Y6R主要来自于巨噬细胞。研究者采用LDLR-/-背景的巨噬细胞P2Y6R条件敲除小鼠（P2Y6Rfl/flLysMcre）构建动脉粥样硬化模型，以P2Y6Rfl/fl作为对照，12周高脂饮食（HFD）喂养后，评估动脉粥样硬化斑块的情况。结果发现，与对照组小鼠相比，巨噬细胞P2Y6R敲除的小鼠中主动脉斑块明显减少。巨噬细胞P2Y6R敲除小鼠主动脉斑块显著减少P2Y6R到底有什么神奇力量？研究者分析了小鼠的巨噬细胞，发现敲除P2Y6R后，巨噬细胞对ox-LDL的摄取显著减少了，并抑制了泡沫细胞的形成。机制上， P2Y6R通过激活PLCβ/SOCE/CALR介导的钙离子信号，引起清道夫受体SR-A表达的上调，从而加速脂质摄取导致巨噬细胞泡沫化。P2Y6R调控巨噬细胞泡沫化由此来看，抑制巨噬细胞P2Y6R很可能是干预动脉粥样硬化的好思路。循着这个思路，研究者通过高通量Glide分子筛选对接体系在药物库中尝试寻找合适的P2Y6R拮抗剂。经过筛选，焦磷酸硫胺素（TPP）、磷酸吡哆醛（PLP）和沙丁胺醇三种小分子脱颖而出。其中，TPP表现出了更强更稳定的P2Y6R拮抗活性，成为研究者的优选。TPP是维生素B1的辅酶形式，天然存在于米糠等食物中，临床上常用于维生素B1缺乏症的治疗。体外实验结果发现，TPP可减少脂质摄取，抑制巨噬细胞泡沫化。给高脂饮食小鼠进行TPP治疗，超生理剂量的TPP（20或40mg/kg）可显著减少小鼠动脉粥样硬化斑块的产生。TPP治疗小鼠的促炎细胞因子水平显著降低，包括IL-1β、TNFα、IL-6、IL-8和TGF-β1等。此外，高剂量TPP并未表现出显著的生理毒性，TPP治疗小鼠体重和摄食量与对照组无显著差异，心脏、肝脏、脾、肺、肾等器官未见损伤。TPP治疗可显著减少高脂饮食小鼠斑块的产生，40mg/kg剂量效果更好总的来说，这项研究首次发现了P2Y6R在动脉粥样硬化进展中的重要作用，巨噬细胞P2Y6R通过PLCβ/SOCE/CALR/SR-A信号通路在泡沫细胞形成和动脉粥样硬化发展中发挥因果作用，有望成为动脉粥样硬化的治疗靶点。更重要的是，TPP作为一种新型P2Y6R抑制剂被发现，超生理剂量的TPP对巨噬细胞泡沫化和动脉粥样硬化具有抑制作用。TPP或可作为预防动脉粥样硬化性心血管疾病高危患者的候选药物。参考文献：[1] Doran AC. Inflammation Resolution: Implications for Atherosclerosis. Circulation Research 2022; 130: 130-148. doi: 10.1161/CIRCRESAHA.121.319822[2] Yehong Li †, Mengze Zhou †, Huanqiu Li †, Chen Dai †, Li Yin, Chunxiao Liu, Yuxin Li, Enming Zhang, Xinli Dong, Hui Ji, and Qinghua Hu. Macrophage P2Y6 receptor deletion attenuates atherosclerosis by limiting foam cell formation through phospholipase Cβ/store-operated calcium entry/calreticulin/scavenger receptor A pathways. European Heart Journal 2023; 00, 1–16. doi.org/10.1093/eurheartj/ehad796本文作者丨代丝雨

临床研究

2023-09-18

·生物谷

ACS Nano：李亚平团队构建三元协同纳米粒，攻破三阴性乳腺癌免疫抑制网络

研究团队首先合成了pH敏感的两亲性聚（β-氨基酯）衍生物，并用其构建了共递送MDSC抑制剂恩替诺特（ENT）和PD-1/PD-L1抑制剂BMS-1的胶束（BEM）。中国科学院上海药物研究所李亚平课题组在 ACS Nano 期刊发表了题为：Breaking tumor immunosuppressive network by regulating multiple nodes with triadic drug delivery nanoparticle 的研究论文。该研究构建了具有级联酸敏感的三元协同纳米粒，其可同时重编程TAM、抑制MDSC和阻断PD-1/PD-L1通路，以TAM、MDSC、CD8+ T细胞为直接调节靶点，利用瘤内免疫网络的串扰实现对NK细胞、树突状细胞和Treg的间接调节，从而全面激活固有和适应性抗肿瘤免疫应答。三元协同纳米粒BEN调节肿瘤免疫微环境治疗三阴性乳腺癌研究团队首先合成了pH敏感的两亲性聚（β-氨基酯）衍生物，并用其构建了共递送MDSC抑制剂恩替诺特（ENT）和PD-1/PD-L1抑制剂BMS-1的胶束（BEM）。随后，将BEM与清道夫受体A（SR-A）的配体硫酸葡聚糖（DXS）通过静电吸附形成复合纳米粒BEN。BEN具有级联酸敏感性，即在pH 7.4时稳定、pH 6.8时DXS外壳脱落、pH 5.5时胶束解离。研究发现，BEN可以实现有效的CAPIR（循环、蓄积、渗透、摄取、释放）过程。带负电的BEN在体内血液循环中保持稳定，有效延长药物半衰期，并通过被动靶向作用在肿瘤部位蓄积。在肿瘤弱酸性微环境中，DXS从BEN上解离，阻断TAM上的SR-A并诱导其向促炎的M1型分化。暴露出的BEM带正电，有利于瘤内渗透和细胞摄取，在溶酶体的酸性环境中，载体聚合物由两亲性变成亲水性，从而导致BEM解离，释放出BMS-1和ENT以阻断PD-1/PD-L1和抑制MDSC。此外，在三种免疫调节药物的协同作用下，BEN重塑了肿瘤免疫微环境，提高瘤内巨噬细胞M1/M2比例、NK细胞数量和CD8+ T细胞数量，下调MDSC和Treg，有效激活固有和适应性抗肿瘤免疫反应，并诱导抗肿瘤免疫记忆，从而抑制肿瘤的生长、转移和复发。上海药物所博士研究生颜雯璐为第一作者，李亚平研究员、尹琦研究员及临港实验室郎天群博士为论文共同通讯作者。该研究得到了科技部重点研发计划、国家自然科学基金、山东省自然科学基金和上海市“扬帆计划”等项目的资助。张江实验室国家蛋白质科学研究（上海）设施和上海药物所冷冻电镜研究中心也在实验中予以支持。

2023-09-17

·生物谷

ACS Nano | 上海药物所构建三元协同纳米粒攻破三阴性乳腺癌的免疫抑制网络

在肿瘤微环境中，以肿瘤细胞和抑制性免疫细胞为节点构成了复杂的免疫抑制网络，各节点之间的信号传递由细胞因子、趋化因子和代谢产物介导。不同的免疫抑制细胞如髓源抑制细胞（MDSC）、肿瘤相关巨噬细胞（TAM）和调节性T细胞（Treg）之间相互促进，并抑制NK细胞和细胞毒性T细胞的作用。免疫疗法已在临床上用于治疗三阴性乳腺癌，但由于肿瘤免疫抑制微环境的代偿调节和药物的非靶向分布，使免疫疗法的效果仍非常有限。基于上述背景，2023年9月10日，中国科学院上海药物研究所李亚平课题组在ACS Nano发表了题为“Breaking tumor immunosuppressive network by regulating multiple nodes with triadic drug delivery nanoparticle”的研究论文。该研究构建了具有级联酸敏感的三元协同纳米粒，其可同时重编程TAM、抑制MDSC和阻断PD-1/PD-L1通路，以TAM、MDSC、CD8+ T细胞为直接调节靶点，利用瘤内免疫网络的串扰实现对NK细胞、树突状细胞和Treg的间接调节，从而全面激活固有和适应性抗肿瘤免疫应答。三元协同纳米粒BEN调节肿瘤免疫微环境治疗三阴性乳腺癌研究人员首先合成了pH敏感的两亲性聚（β-氨基酯）衍生物，并用其构建了共递送MDSC抑制剂恩替诺特（ENT）和PD-1/PD-L1抑制剂BMS-1的胶束（BEM）。随后，将BEM与清道夫受体A（SR-A）的配体硫酸葡聚糖（DXS）通过静电吸附形成复合纳米粒BEN。BEN具有级联酸敏感性，即在pH 7.4时稳定、pH 6.8时DXS外壳脱落、pH 5.5时胶束解离。BEN具有级联酸敏感性研究发现，BEN可以实现有效的CAPIR（循环、蓄积、渗透、摄取、释放）过程。带负电的BEN在体内血液循环中保持稳定，有效延长药物半衰期，并通过被动靶向作用在肿瘤部位蓄积。在肿瘤弱酸性微环境中，DXS从BEN上解离，阻断TAM上的SR-A并诱导其向促炎的M1型分化。暴露出的BEM带正电，有利于瘤内渗透和细胞摄取，在溶酶体的酸性环境中，载体聚合物由两亲性变成亲水性，从而导致BEM解离，释放出BMS-1和ENT以阻断PD-1/PD-L1和抑制MDSC。此外，在三种免疫调节药物的协同作用下，BEN重塑了肿瘤免疫微环境，提高瘤内巨噬细胞M1/M2比例、NK细胞数量和CD8+ T细胞数量，下调MDSC和Treg，有效激活固有和适应性抗肿瘤免疫反应，并诱导抗肿瘤免疫记忆，从而抑制肿瘤的生长、转移和复发。BEN通过调节肿瘤免疫微环境抗肿瘤上海药物所博士研究生颜雯璐为第一作者，李亚平研究员、尹琦研究员及临港实验室郎天群博士为本文共同通讯作者。该研究得到了科技部重点研发计划、国家自然科学基金、山东省自然科学基金和上海市“扬帆计划”等项目的资助。张江实验室国家蛋白质科学研究（上海）设施和上海药物所冷冻电镜研究中心也在实验中予以支持。全文链接：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acsnano.3c03387会议推荐会议详情会议名称：2023（第14届）细胞与基因治疗研讨会暨抗体工程与创新免疫治疗技术论坛主办单位：生物谷、梅斯医学、同济大学附属同济医院、南京可缘大会时间：9月22-23日大会地点：上海大会规模：1500人2010年至今，生物谷联合各合作单位已经顺利召开了13届细胞与基因治疗研讨会，与全球致力于细胞治疗行业同仁们一同成长沉淀，在提供行业信息交流平台的同时，也为基础研究提供了技术/产品等产业化的孵化平台。基于此，本届会议将继续以转化医学为切入点，以基础研究与临床应用相结合，针对细胞治疗的临床前沿研究、临床监管、治疗规范、细胞治疗安全性，免疫细胞新型疗法、实体瘤治疗、干细胞与癌症、抗体药物、核酸药物、基因编辑、肿瘤免疫治疗等热门议题进行讨论，诚邀国内外产学研医专家共聚，共绘产业发展新蓝图！长按识别二维码立即报名参会

免疫疗法细胞疗法