更新于：2024-09-19

FSTL1

更新于：2024-09-19

基本信息

别名

follistatin like 1、Follistatin-like protein 1、Follistatin-related protein 1

+ [6]

简介

Secreted glycoprotein that is involved in various physiological processes, such as angiogenesis, regulation of the immune response, cell proliferation and differentiation (PubMed:29212066, PubMed:22265692). Plays a role in the development of the central nervous system, skeletal system, lungs, and ureter (By similarity). Promotes endothelial cell survival, migration and differentiation into network structures in an AKT-dependent manner. Also promotes survival of cardiac myocytes (By similarity). Initiates various signaling cascades by activating different receptors on the cell surface such as DIP2A, TLR4 or BMP receptors (PubMed:20054002, PubMed:22265692).

关联

项与 FSTL1 相关的药物

PFI-103

靶点

FSTL1

作用机制

FSTL1 inhibitors

在研机构

Pharma Foods International Co., Ltd.

原研机构

Japanese National Cancer Center

在研适应症

肿瘤

非在研适应症

骨肉瘤 [+1]

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 FSTL1 相关的临床结果

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100 项与 FSTL1 相关的转化医学

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0 项与 FSTL1 相关的专利（医药）

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512

项与 FSTL1 相关的文献（医药）

2024-11-01·Current Cardiology Reviews

The Association between Serum Follistatin-like Proteins and Cardiovascular Diseases: A Systematic Review and Meta-analysis

Article

作者: Sahebkar, Amirhossein ; Ahmadzadeh, Amir Mahmoud ; Aliakbarian, Mohsen ; Shabestari, Mahmoud Mohamadzadeh ; Arjmand, Mohammad-Hassan ; Khodashahi, Rozita

Background:Follistatin-like proteins (FSTLs) are adipomyokines secreted by adipocytes and myocytes. Previous studies have reported an increase in circulating FSTL1 levels in response to cardiovascular injuries. In this study, we conducted a systematic review and metaanalysis to assess the association between circulating FSTLs and Cardiovascular Diseases (CVDs).Methods:We performed a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase databases. After screening the articles, we selected eligible studies, extracted relevant data, and calculated the pooled Standardized Mean Difference (SMD). We also conducted a sensitivity analysis to identify sources of heterogeneity and assessed publication bias.Results:Among the 577 articles initially retrieved, we included 5 studies comprising a total of 941 cases with CVDs and 446 controls. All included studies measured FSTL1 levels. The pooled SMD analysis revealed a significant difference in circulating FSTL1 levels between subjects with CVDs and control groups (SMD = 0.853, 95% CI = 0.158-1.548, P = 0.016). Heterogeneity was primarily attributed to a single study that measured FSTL1 levels in heart failure patients with preserved ejection fraction. No publication bias was observed.Conclusion:Our findings demonstrate significantly higher levels of FSTL1 in patients with CVD compared to control subjects. This suggests that FSTL1 may have potential as a diagnostic and prognostic biomarker in CVDs. However, further well-designed studies are needed to validate its clinical utility.

2024-10-01·Biochimie

A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing

Article

作者: Vijayarengan, Monisha ; Suresh, Anagha Priya ; Sundaram, Gopinath M ; Soundaram, Rajendran ; Gnanesh Kumar, B S ; Aggarwal, Pooja

Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using in-silico analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 in vitro. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely via its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, trans-dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing.

2024-08-01·Inflammation

FSTL1 Accelerates Nucleus Pulposus Cell Senescence and Intervertebral Disc Degeneration Through TLR4/NF-κB Pathway

Article

作者: Zhang, Ren-Jie ; Ding, Jing-Yu ; Liu, Xiao-Ying ; Yan, Xu ; Jia, Chong-Yu ; Zhang, Hua-Qing ; Kang, Liang ; Shen, Cai-Liang

Intervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP), and inflammatory factors play crucial roles in its pathogenesis. Follistatin-like 1 (FSTL1) has been reported to induce an inflammatory response in chondrocytes, microglia and preadipocytes, but its role in the pathogenesis of nucleus pulposus cell (NPC) degeneration remains unclear. In this study, we mainly utilized an acidosis-induced NPC degeneration model and a rabbit puncture IVDD model to investigate the role of FSTL1 in IVDD both in vitro and in vivo. We confirmed that FSTL1 expression significantly increased in nucleus pulposus (NP) tissues from IVDD patients and rabbit puncture IVDD models. The expression levels of FSTL1 were significantly increased in all three models of NPC degeneration under harsh microenvironments. In addition, recombinant human FSTL1 (rh-FSTL1) was found to upregulate the expression of p16 and p21, increase the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells, induce senescence-related secretory phenotypes (SASP), and downregulate extracellular matrix (ECM) protein expressions, leading to an imbalance in ECM metabolism destructions. Conversely, silencing of FSTL1 by small interfering RNA (siRNA) ameliorated senescence of NPCs associated with inflammation in IVDD. Furthermore, Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway plays a crucial role in regulating NPC senescence through FSTL1 regulation. Inhibition of TLR4 expression partly reversed the effects of rh-FSTL1 on NPC senescence-associated inflammation. Finally, rabbit IVDD model experiments demonstrated that the specific FSTL1 siRNA markedly repressed the development of IVDD. These findings may offer a therapeutic approach for mitigating inflammation-induced senescence associated with IVDD.

项与 FSTL1 相关的新闻（医药）

2023-03-22

·BioSpace

Regencor Expands Scientific Advisory Board

SAN MATEO, Calif., March 22, 2023 /PRNewswire/ -- Regencor Inc. a life sciences company that is focused on the development of therapies for treatment of cardiovascular disease, today announced it has appointed Philip Janiak, Ph.D. and Ken Mahaffey, M.D. to its Scientific Advisory Board. They join Nabil Dib, M.D. who was previously appointed to the Regencor S.A.B. Dr. Ken Mahaffey, M.D. is a professor of cardiovascular medicine at the Stanford University School of Medicine. His primary area of research is the design and execution of multicenter clinical trials, focusing on analyses of important clinical cardiac outcome measures using large patient databases. Current research activities include standardization of the definition of myocardial infarction used in clinical trials, the adjudication of suspected clinical endpoint events by Clinical Event Committees (CEC), and the efficient operational conduct of large multinational clinical trials. He has led or served on the Executive Committees for many cardiovascular outcome trials, over 125 Clinical Endpoint Committees, and multiple Data Safety Monitoring Boards. He has worked with the FDA and is a consultant for the Endocrinologic and Metabolic Drugs Advisory Committee. Dr. Mahaffey received a B.S. in Chemistry from Stanford University, followed by his M.D. from the University of Arizona Health Sciences Center. He completed a cardiology fellowship at Duke, including research training in the Duke Databank for Cardiovascular Disease. He is recognized as an international leader in the design and execution of large-scale cardiovascular trials. Philip Janiak, PhD, received his PhD degree in Cardiovascular Pharmacology from the University of Iowa, USA (1989) and graduated from the Faculty of Pharmacy (Paris XI University) in 1984. He started his career at Servier where he contributed to the discovery of ivabradine as a co-inventor. Until the end of 2020 he was the head of Cardiovascular Research at Sanofi focusing on the development of new treatments in selected areas of unmet medical need where emerging science and a better understanding of human disease biology intersects with heart failure at the molecular level. During his career he developed extensive experience in the management of international R&D groups and in leading multiple research collaborations with biopharmaceutical companies such as MyoKardia, and academic institutions such as IMI. He is currently the CEO of Corteria Pharmaceuticals "I am thrilled to join Regencor's SAB and delighted to be able to provide guidance to the team," said Dr. Mahaffey. "The Company has generated compelling data on the use of unglycosylated FSTL1, and I am eager to collaborate with, and help guide the scientific team regarding the Company's future development plans." "Regencor is uniquely positioned to advance treatments for myocardial infarction and to help prevent the progression to heart failure." said Dr. Janiak. "I look forward to working with this team to help shape new clinical approaches for the treatment of cardiovascular disease." "We are delighted and honored to have such accomplished scientific leaders join our Scientific Advisory Board," said Sean Edwards, Chief Executive Officer of Regencor. "Dr. Mahaffey and Dr. Janiak bring tremendous expertise in the field of cardiovascular disease. Feedback and collaboration with our SAB will be a vital component of our efforts to continue the development of our unique therapies." For more information on Regencor, please visit About Regencor Inc. Regencor, Inc. is a life sciences company focused on the development of therapeutics for cardiovascular disease. REG 101 is a proprietary recombinant protein that has been shown to stimulate the proliferation of cardiomyocytes post myocardial infarction. The regenerative properties of REG 101 have been demonstrated in several in-vivo large animal studies. The Company is targeting initial indications of acute myocardial infarction and also chronic heart failure. View original content to download multimedia: SOURCE Regencor, Inc.

高管变更AHA会议

2023-03-10

·靶点社

攻关活细胞分析技术，CNS发表竟如此简单？

细胞实验是最基本、最普遍的生物分析手段之一，从细胞形态、定位、生长趋势、功能及相互作用等方向提供生物学信息。自从1674年Anton van Leeuwenhoek通过基础显微镜首次观察到活细胞以来，活细胞分析技术不断更新迭代，并在生物医学界的进步和发展中发挥着举足轻重的作用。随着医药大健康成为国家战略，高校院所、生物技术公司及制药企业等研究人员均在基础生命科学领域进行更广泛和更深入的研究。培养箱能够保证稳定的CO2和湿度等要求，确保适合的细胞培养条件，使细胞处于最佳生长状态。常规的细胞分析实验需要频繁进出细胞间，将细胞拿出培养箱用显微镜进行观察后再放回培养箱。可是存在的问题也是显而易见的：错失细胞的动态变化：细胞的行为是动态的，细胞群体变化、结构和功能变化可能在很长的一段时间内发生。单个时间的终点检测是片面的，甚至不可靠。脆弱的细胞，培养不易，易受干扰：如敏感的神经细胞、干细胞、原代细胞等，易受到干扰，应该尽量减少移动，避免固定和清洗步骤等，尽量维持一个稳定的生理环境。细胞分析复杂困难：常见的各类成像分析软件，操作复杂，步骤多，甚至需要深入的专业知识。赛多利斯推出Incucyte®实时活细胞分析系统，可以置于培养箱中直接对细胞进行实时、动态、连续的长时间监测，确保细胞免受干扰，并将细胞的“精彩故事”变成mini电影呈现出来，提供更生动、更有趣的细胞洞察。目前有超过13000篇相关文献均使用Incucyte®系统进行细胞学研究，其中CNS顶刊超过200篇，广泛涉及肿瘤、免疫、药物开发、代谢、干细胞、再生医学、疾病感染等诸多领域，涵盖了细胞增殖、迁移/划痕/趋化、细胞毒性、凋亡、侵袭、细胞杀伤、3D肿瘤球、神经生长等多种应用。**点击查看大图Incucyte®应用领域Incucyte®应用方向在此，我们甄选出五篇使用Incucyte®的高引CNS文章，详细介绍实时活细胞分析技术的典型应用。1Science：免疫细胞杀伤应用领域：肿瘤学视频来源：Han-Chuang Hsiue et al. Science 2021, 05, 371(6533)约翰霍普金斯大学的Shibin Zhou等人[1]开发出一种靶向TP53突变基因的双特异性单链抗体H2-scDb。采用Incucyte®的NucLight green快速染料标记1 × 104个TYK-nu细胞，96孔板放置4h，然后加入2 × 104个或5 × 104个T细胞和激活剂scDb（anti-CD3ε scFv，单链双特异性抗体形式）进行共培养。不断减少的绿色荧光信号，表明激活的T细胞具有显著的免疫杀伤作用。同时，通过Incucyte®系统的10×物镜连续拍摄120h，计算每孔中每mm2的gfp阳性对象数量，发现H2-scDb介导的细胞毒性同样通过TP53的破坏而减轻。2Nature：神经细胞吞噬及分化应用领域：神经科学研究中枢神经系统（CNS）损伤和疾病会强烈诱导星形胶质（Astrocytes）细胞通过增生可形成胶质“瘢痕”。斯坦福大学Shane A. Liddelow等人[2]研究发现了一种星形胶质细胞亚型（A1）。A1由激活的小胶质细胞通过分泌Il-1α、TNF和C1q诱导生产，并参与多种神经退行性疾病，包括阿尔茨海默氏症、亨廷顿氏症和帕金森氏症、肌萎缩性侧索硬化症和多发性硬化症。A1没有促进神经元生存、生长、突触发生和吞噬的能力，但可以诱发神经元和少突胶质细胞的死亡。当阻断A1的形成时，中枢神经系统神经元的死亡被阻止了。这为神经退行性疾病的新疗法提供机会。此研究中研究人员通过pHrodo red染料突触小体及髓鞘碎片来研究大鼠神经细胞Astrocytes对其的吞噬能力。在Incucyte®的20×物镜从24孔板中获取9张图像，检测比较吞噬能力。同时还在明场视野下监控OPCs (oligodendrocyte precursor cells)细胞的生长分化过程。3Nature：划痕实验及细胞迁移应用领域：转化医学伤口愈合涉及细胞迁移、增殖和细胞外基质重塑，以及转化生长因子-β（TGF-β）的刺激。其中角质细胞（Keratinocyte）的迁移和上皮形成对伤口愈合至关重要。新加坡国立大学Prabha Sampath等人研究发现[3]，microRNA-198 (miR-198)表达后会通过靶向和抑制DIAPH1, PLAU 以及LAMC2来抑制角质细胞迁移，而FSTLI恰好相反，能够促进角质细胞迁移。TGF-β1作为关键的转录调节开关，能够通过降低KSRP(KH型剪接调节蛋白)的产生来抑制miR-198的生成，并间接促进FSTL1的表达。这一发现为改善病人伤口愈合疗法提供新的途径。在此研究中，Incucyte®被用于划痕实验及细胞迁移的实时监测。角质细胞转染48h后，使用Incucyte® wound maker制造划痕，用Incucyte®拍照监测创伤愈合情况。上图和视频分别为不同时间点转染对照siRNA以及fstl1特异性siRNA的细胞迁移图像(n=5)。在24h时，对照转染细胞的伤口完全愈合，而敲除FSTL1后细胞的伤口仅愈合15±5%。Incucyte®监测过表达的对照miRNA角质细胞的划痕实验Incucyte®监测过表达的miR-198角质细胞的划痕实验视频来源：Sundaram, G., et al. Nature 2013, 495, 103–1064Cell：细胞毒性及细胞凋亡应用领域：免疫学RIPK3（受体相互作用蛋白激酶-3）激活MLKL，导致质膜（PM）破坏和一种受调控的坏死性凋亡。St. Jude儿童研究医院的Douglas R. Green等人[4] 发现激活MLKL导致破碎的、带有暴露的磷脂酰丝氨酸（PS）的PM气泡产生，这些气泡从原本完整的细胞表面释放出来。ESCRT-III机制是形成这些气泡的必要条件，当MLKL的激活受到限制或被逆转时，它能维持细胞的生存。在坏死细胞死亡的条件下，ESCRT-III控制质膜完整持续的时间。由于ESCRT-III的作用，坏死细胞可以表达趋化因子和其他调节分子，促进CD8+T细胞的抗原交叉刺激。研究人员通过将Sytox-Green标记的L929细胞死亡刺激物转染到L292细胞中，用Incucyte®监控不同时间点以及不同抑制剂的情况下的细胞死亡情况（% SytoxGreen），并确认ESCRT-III可以对抗坏死性凋亡（Necroptosis）。5Nature：细胞增殖应用领域：病毒学德国BioNTech公司的Ugur Sahin等人[5]开发的BNT162b2是全球首个上市的mRNA新冠疫苗，并取得了显著的治疗效果。在该疫苗的临床前研究中，采用Incucyte®系统建立了假病毒血清抑制试验。Vero-76细胞接种于96孔板中，小鼠血清倍比稀释后与VSV-SARS-CoV-2假病毒悬液(4.8 × 103感染滴度/mL)混匀室温预孵育10分钟，然后转移到Vero-76细胞中，37℃下孵育20 h。在Incucyte®中培养，通过4×物镜并进行明场全孔扫描和GFP荧光扫描。计算pVNT50（与无血清假病毒阳性对照相比，可减少每孔50%GFP阳性感染细胞数的最低血清稀释度）来评价疫苗血清的病毒抑制能力。Incucyte®实时活细胞成像分析为以上的细胞学实验开展和数据分析提供了高效便捷的工具。2020年，Science副刊《Science Immunology》还曾专门发布独家文章，对Incucyte®的相关应用进行聚焦和分析。Nature 子刊，攻坚实体瘤，CAR-T疗法寻突破2021年顶级医学期刊nature medicine发布了CAR-T之父Carl June最新研究，也是首个CAR-T治疗实体瘤临床研究结果。CAR-T细胞疗法治疗实体瘤不再是停留在理论与展望阶段，而是进入了前列腺癌治疗的Ⅰ期临床研究，并且证实了抗TGF-β的CAR-T细胞疗法治疗转移性去势抵抗性前列腺癌这一实体瘤是安全可行的。我们看到了CAR-T细胞疗法治疗实体瘤取得的重大突破，但举步维艰的过去同样值得铭记和反思。实体瘤本身及其微环境的特殊性为细胞治疗带来了巨大挑战，一方面，实体瘤细胞抗原的异质性以及特异性肿瘤抗原的缺乏使CAR细胞难以对肿瘤细胞进行精准的靶向性识别和杀伤；另一方面，实体瘤特殊的肿瘤微环境，包括异常血管结构和基质成分组成的第一道物理屏障，以及TME 中多种免疫抑制细胞、抑制性免疫及代谢分子组成的二次屏障，使得细胞治疗药物难以浸润肿瘤组织。但随着对肿瘤生物学和免疫学的进一步研究，科学家开发了一些应对策略克服这些障碍，使得细胞疗法应用于实体瘤成为可能。2023年3月23日14:00-15:30药融圈联合赛多利斯举办本次线上研讨会，邀请2位行业专家，就细胞治疗在实体瘤治疗方面的新技术、新思想展开分享，欢迎观看。扫码报名识别二维码点击【观看直播】即可报名点击开播提醒不错过关于赛多利斯赛多利斯集团是生命科学研究和生物制药行业的领先国际合作伙伴。该集团的实验室产品与服务板块用心研究创新型实验室仪器和耗材，致力于满足制药和生物制药公司以及学术研究机构旗下研究和质量控制实验室的需求。生物工艺解决方案板块推出了广泛的产品组合，专注于一次性解决方案，帮助客户安全高效地制造生物技术药物和疫苗。该集团平均每年以两位数的速度增长，并积极收购互补技术，以实现产品组合的常规扩展。关于药融圈药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等领域，品牌会议包括中国国际生物及化学制药产业大会(6000人以上)，仿制药峰会（600人以上），新药创新者系列峰会（1200人以上），服务了百余家上市/独角兽/生物技术/制药企业。药融圈生物医药生态圈合作伙伴：凌凯医药、福抗药业、汉瑞药业、深圳华溶、健元医药、济民可信、则正医药、亚瑟医药、苏州亚科、青木制药、昭衍新药、阳光德美、成都先导、方达医药、博腾制药、百诚医药、慧泽医药、艾奇西医药、汉康医药、美迪西、南京生命能、海纳医药、江苏诺泰澳赛、赛默飞、梅特勒、ProteinSimple、赛多利斯、思拓凡、苏州晶云、中科普瑞昇、康日百奥、宜明细胞、珠海亿胜、格林泰科、三优生物、百奥赛图、杭州皓阳、申基生物、金斯瑞蓬勃、原启生物、翰思生物、益方生物、爱思益普、迈威生物、华津医药、晶泰科技、英矽智能、嘉树医疗、浙江齐蓁、简然实验室、毕得医药、汉库医药、川成医药、恒兴医药、华益药业、博诺康源、伊诺凯……-参考文献-Han-Chuang Hsiue et al. 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