更新于：2024-09-19

STAB2

更新于：2024-09-19

基本信息

别名

190 kDa form stabilin-2、190 kDa hyaluronan receptor for endocytosis、DKFZP434E0321

+ [13]

简介

Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Acts also, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed 190 kDa form also functions as an endocytosis receptor for heparin internalization as well as HA and CS.

关联

项与 STAB2 相关的药物

HG-1263

靶点

STAB2 x 清道夫受体

作用机制

STAB2 modulators [+1]

在研机构-

原研机构

Human Genome Sciences, Inc.

在研适应症-

非在研适应症

心血管疾病 [+3]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 STAB2 相关的临床结果

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100 项与 STAB2 相关的转化医学

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0 项与 STAB2 相关的专利（医药）

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226

项与 STAB2 相关的文献（医药）

2024-08-09·Успехи геронтологии

HYALURONAN RECEPTORS: ROLE IN AGING AND AGE-ASSOCIATED PROCESSES

Review

作者: Zubareva, T S ; Kvetnaya, T V ; Khabarov, V N ; Drobintseva, A O ; Mironova, E S

2024-06-18·ACS Omega

Global Gene Expression Profiling and Bioinformatics Analysis Reveal Downregulated Biomarkers as Potential Indicators for Hepatocellular Carcinoma

Article

作者: Mestareehi, Aktham

Objective: The study aimed to elucidate the significance of CLEC4G, CAMK2β, SLC22A1, CBFA2T3, and STAB2 in the prognosis of hepatocellular carcinoma (HCC) patients and their associated molecular biological characteristics. Additionally, the research sought to identify new potential biomarkers with therapeutic and diagnostic relevance for clinical applications. Methods and Materials: We utilized a publicly available high throughput phosphoproteomics and proteomics data set of HCC to focus on the analysis of 12 downregulated phosphoproteins in HCC. Our approach integrates bioinformatic analysis with pathway analysis, encompassing gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the construction of a protein-protein interaction (PPI) network. Results: In total, we quantified 11547 phosphorylation sites associated with 4043 phosphoproteins from a cohort of 159 HCC patients. Within this extensive data set, our specific focus was on 19 phosphorylation sites displaying significant downregulation (log₂ FC ≤ -2 with p-values < 0.0001). Remarkably, our investigation revealed distinct pathways exhibiting differential regulation across multiple dimensions, including the genomic, transcriptomic, proteomic, and phosphoproteomic levels. These pathways encompass a wide range of critical cellular processes, including cellular component organization, cell cycle control, signaling pathways, transcriptional and translational control, and metabolism. Furthermore, our bioinformatics analysis unveiled noteworthy insights into the subcellular localizations, biological processes, and molecular functions associated with these proteins and phosphoproteins. Within the context of the PPI network, we identified 12 key genes CLEC4G, STAB2, ADH1A, ADH1B, CAMK2B, ADH4, CHGB, PYGL, ADH1C, AKAP12, CBFA2T3, and SLC22A1 as the top highly interconnected hub genes. Conclusions: The findings related to CLEC4G, ADH1B, SLC22A1, CAMK2β, CBFA2T3, and STAB2 indicate their reduced expression in HCC, which is associated with an unfavorable prognosis. Furthermore, the results of KEGG and GO pathway analyses suggest that these genes may impact liver cancer by engaging various targets and pathways, ultimately promoting the progression of hepatocellular carcinoma. These results underscore the significant potential of CLEC4G, ADH1B, SLC22A1, CAMK2β, CBFA2T3, and STAB2 as key contributors to HCC development and advancement. This insight holds promise for identifying therapeutic targets and charting research avenues to enhance our understanding of the intricate molecular mechanisms underlying hepatocellular carcinoma.

2024-06-01·Cell Biochemistry and Biophysics

Stabilin-2 mediated apoptotic cell phagocytosis induces interleukin-10 expression by p38 and Pbx1 signaling

Article

作者: Jo, Han-Seul ; Kim, Ha-Jeong

AbstractApoptotic cell death occurs under normal physiological conditions, such as development, tissue remodeling, and inflammation. Appropriate removal of apoptotic cells by phagocytes and the secretion of anti-inflammatory cytokines such as IL-10 are important mechanisms for maintaining tissue homeostasis. Apoptotic cell phagocytosis is mediated by several phosphatidylserine recognition receptors on non-professional or professional phagocytes, such as neighboring epithelial cells or macrophages. Stabilin-2 is reported as a phosphatidylserine recognition receptor for apoptotic cell phagocytosis, and its downstream signaling pathway for cytoskeletal rearrangement for phagocytosis is well known. However, the mechanisms for stabilin-2-mediated IL-10 production has not yet been reported. In this study, we aimed to investigate stabilin-2 receptor-mediated IL-10 transcription regulation signaling pathway.

项与 STAB2 相关的新闻（医药）

2022-08-30

·生物谷

Nature系列综述：胞葬作用的概念与成药机会

当前，将免疫与代谢联系起来的复杂相互作用网络已成为药物设计热点。每天大约有2000 - 3000亿个细胞在人体内死亡、周转，细胞死亡有多种形式，在稳态条件下，主要通过caspase依赖的凋亡（apoptosis）过程。尽管凋亡细胞经常大量产生，但在体内组织中很难观察到。这是因为细胞死亡耦联胞葬（efferocytosis）过程——即吞噬细胞高效吞噬、清除凋亡细胞的过程 [1]。胞葬对于人体维持正常稳态平衡十分关键。影响胞葬的因素有吞噬细胞与凋亡细胞的比例、吞噬细胞的性质(专业或非专业)、死亡细胞的大小、特定空间位置的死亡率，以及促进胞葬的刺激性信号分子 [2]。胞葬是一个多步骤的生理过程，加强这些步骤中的任何一个都可以促进胞葬，同时抑制组织炎症。以下将简述关键的信号分子和针对该步骤的治疗策略 [3]。凋亡细胞释放多种“Find Me”信号。如核苷酸ATP、UTP，膜脂质LysoPC，趋化因子CX3CL1和新发现的特殊代谢物多胺等 [4]。这些可溶性因子具有双重作用：一是作为吞噬细胞向凋亡细胞迁移的吸引信号；二是调节吞噬细胞骨架，增强吞噬受体的表达和消化机制 [5]。另外，这些信号也促进吞噬细胞的再生和抗炎特性。随着质谱成像技术的快速发展，现在已经可以破译不同组织环境中每一种“Find Me”信号的相对重要性和丰度，这有助于了解将来如何“对症下药”。目前，“体外光疗”（ECP）已被广泛用于促进器官移植。多种实验移植模型都表明，将供体凋亡细胞处理后输入受体，移植物的接受度显著提高 [6]，这可能与凋亡细胞释放的抗炎信号有关。因此，通过激活smell phase的相关通路，促进凋亡细胞释放可溶性介质，具有治疗炎症性疾病的应用前景（图1）。吞噬细胞特异性识别凋亡细胞表面暴露的“Eat Me”信号 [7]，最典型的、进化保守的“吃我”信号是暴露在质膜外层上的磷脂酰丝氨酸（Phosphatidylserine, PS），其他信号包括钙网蛋白、annexin 1、氧化低密度脂蛋白、血栓反应蛋白1结合位点和补体蛋白C1q或C3b结合位点暴露在凋亡细胞表面的PS可通过受体直接或间接结合。直接结合的受体包括脑特异性血管生成抑制剂1 (BAI1)、T细胞免疫球蛋白粘蛋白受体TIM1-TIM4和Stabilin 2，而酪氨酸激酶Tyro3/Axl/Mer受体通过一些可溶性桥接分子与PS间接结合。凋亡细胞与吞噬细胞上受体的结合触发了复杂的细胞骨架重排，促进其形成吞噬体，然后与溶酶体融合，溶酶体内含有许多pH敏感的降解酶，从而促进凋亡细胞内容物的释放和生物分解。关键的胞葬下游信号通路涉及GTPase RAC1，它通过ELMO和DOCK蛋白被激活，以增强肌动蛋白的重构和吞噬杯的形成。由于PS受体的普遍性，其可能成为多种病理过程的治疗靶点，临床试验中已有多种方法可以改变PS受体的活性或有效性。利用基因编辑技术（如CRISPR和AAV介导的基因传递）调节PS受体的表达有助于疾病模型的建立。PS受体信号的小分子抑制剂作为癌症治疗药物已进入临床试验的晚期。另外，在肿瘤和动脉粥样硬化疾病中，CD47——经典的“don't eat me”信号经常在清除凋亡细胞缺陷的细胞中过表达，而阻断CD47–SIRP1相互作用可以用于治疗（图2）。本阶段对吞噬细胞获取碳水、蛋白质、核苷酸等营养物质至关重要。

免疫疗法小分子药物

2022-07-18

·生物谷

Hepatology: ALK1控制遗传性出血性肝毛细血管扩张症

该研究证实了肝内皮细胞ALK1信号保护器官特异性内皮细胞分化和血管分泌信号，防止血管畸形的发生。遗传性出血性毛细血管扩张症(HHT)是一种常染色体显性遗传病，可导致多器官血管畸形。HHT最常见的症状是鼻出血、毛细血管扩张和内脏损害。HHT的患病率较低，为1：5000，因此，诊断通常会延迟多年。复发性鼻出血影响约90%的HHT患者，是最常见和最明显的主诉。然而，肝脏等内部器官的畸形和分流与长期预后更相关，因为它们最终可能导致心力衰竭。在遗传性出血性毛细血管扩张症(HHT)中，严重的肝血管畸形与编码ALK1的激活素A受体样1型(ACVRL1)基因突变有关，ALK1是BMP9/BMP10的受体，调节血管发育。在这里，研究者建立了一种新的HHT小鼠模型，该模型只涉及肝脏，并具有足够的预期寿命，以研究ALK1信号在肝脏血管形成和代谢功能中的作用。图片来源: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35776660/ 近日，来自莱顿大学医学中心的研究者们在Hepatology杂志上发表了题为“ALK1 controls hepatic vessel formation, angiodiversity, and angiocrine functions in hereditary hemorrhagic telangiectasia of the liver”的文章，该研究证实了肝内皮细胞ALK1信号保护器官特异性内皮细胞分化和血管分泌信号，防止血管畸形的发生。长期存活的Alk1HEC-KO HHT模型为开发这种严重疾病的靶向治疗提供了新的机会。研究者将肝窦内皮细胞(LSEC)选择性Cre缺失品系Stab2-iCreF3与Acvrl1-Flobled小鼠杂交，获得LSEC特异性Acvrl1缺陷小鼠(Alk1HEC-KO)。Alk1HECKO小鼠表现出肝脏血管畸形和肝后血流增加，导致右室容量超负荷。转录学分析表明，在LSEC和中心静脉同一性的代价下，诱导了前血管生成/TIP细胞基因组和肝血管的动脉化。LSEC血管因子Wnt2、Wnt9b和Rspo3的缺失导致了Alk1HEC-KO小鼠和HHT患者肝脏标本中代谢肝区带的破坏。此外，在Alk1HEC-KO肝内皮细胞中，PrND和胎盘生长因子(PGF)表达上调，代表了HHT器官特异性发病的新候选基因。在LSEC体外，刺激或抑制ALK1信号反向调节DNA结合抑制物(ID)1-3，已知的Alk1转录靶点。对ALK1信号的刺激和对ID1-3功能的抑制证实了BMP9/ALK1/ID轴对WNT2和Rsp3的调节。机制总结图图片来源: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35776660/ 本研究的小鼠HHT模型与人类疾病之间的显著相似性证实了Alk1HEC-KO小鼠是研究HHT在肝脏中的发展以及在疾病发展的不同阶段开发和验证新的治疗策略的有价值的工具。在HHT晚期，由于肝脏分流和容量超负荷，心力衰竭是一种严重的并发症，这也反映在研究者HHT模型中。（生物谷 Bioon.com）参考文献 Christian David Schmid et al. ALK1 controls hepatic vessel formation, angiodiversity, and angiocrine functions in hereditary hemorrhagic telangiectasia of the liver. Hepatology. 2022 Jul 1. doi: 10.1002/hep.32641.