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更新于：2025-05-07

CC10

更新于：2025-05-07

基本信息

别名

CC10、CC16、CCPBP

+ [13]

简介

Binds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.

关联

项与 CC10 相关的药物

Uteroglobin

靶点

CC10

作用机制

CC10刺激剂

在研机构-

原研机构

Therabron Therapeutics, Inc.

在研适应症-

非在研适应症

支气管肺发育不良 [+1]

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

项与 CC10 相关的临床试验

EUCTR2015-000253-21-FR

/ Unknown status临床2期

Efficacy of recombinant human club (clara) cell 10kDa protein (CC10) administered to premature neonates with respiratory distress syndrome.

开始日期-

申办/合作机构

Therabron Therapeutics, Inc.

NCT01941745

/ Completed临床2期IIT

Efficacy of Recombinant Human Clara Cell Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome

Bronchopulmonary Dysplasia (BPD) is a multi-factorial disease process that is the end result of an immature, surfactant deficient lung that has been exposed to hyperoxia, mechanical ventilation and infection. These conditions initiate an inflammatory response characterized by elevated inflammatory cell infiltrates and proinflammatory cytokines that lead to the development of significant acute and chronic lung injury.
The study drug, rhCC10, is a recombinant version of natural human CC10 protein. Native CC10 is produced primarily by non-ciliated respiratory epithelial cells, called Clara cells and is the most abundant protein in the mucosal fluids in normal healthy lungs.
The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and anti-inflammatory effects of a single intratracheal (IT) dose of rhCC10 to intubated premature infants receiving positive pressure ventilation for treatment of respiratory distress syndrome (RDS) to prevent long term respiratory complications referred to as bronchopulmonary dysplasia, and, more recently, as Chronic Pulmonary Insufficiency of Prematurity (CPIP; asthma, cough, wheezing, multiple respiratory infections).
CC10 regulates inflammatory responses and protects the structural integrity of pulmonary tissue while preserving pulmonary mechanical function during various insults (eg. viral infection, bacterial endotoxin, ozone, allergens, hyperoxia). Together these properties suggest that administration of rhCC10 may help to facilitate development of normal airway epithelia and prevent the inflammation that leads to CPIP in these infants.
This study is funded by the FDA Office of Orphan Product Development (OOPD).

开始日期2013-10-01

申办/合作机构

Tufts Medical Center, Inc.

[+5]

NCT01473264

/ Completed临床1/2期

Safety and Tolerability of Recombinant Human Clara Cell 10kDa Protein (rhCC10) Delivered Intratracheally to Premature Neonates With Respiratory Distress Syndrome

Bronchopulmonary Dysplasia (BPD) is a multi-factorial disease process that is the end result of an immature, surfactant deficient lung that has been exposed to hyperoxia, mechanical ventilation and infection. These conditions initiate an inflammatory response characterized by elevated inflammatory cell infiltrates and proinflammatory cytokines that lead to the development of significant acute and chronic lung injury.
The study drug, rhCC10, is a recombinant version of natural human CC10 protein. Native CC10 is produced primarily by non-ciliated respiratory epithelial cells, called Clara cells and is the most abundant protein in the mucosal fluids in normal healthy lungs.
The purpose of this study was to evaluate the pharmacokinetics, safety, tolerability and anti-inflammatory effects of a single intratracheal (IT) dose of rhCC10 to intubated premature infants receiving positive pressure ventilation for treatment of respiratory distress syndrome (RDS) to prevent long term respiratory complications referred to as bronchopulmonary dysplasia, and, more recently, as chronic respiratory morbidity (CRM; asthma, cough, wheezing, multiple respiratory infections).
CC10 regulates inflammatory responses and protects the structural integrity of pulmonary tissue while preserving pulmonary mechanical function during various insults (eg. viral infection, bacterial endotoxin, ozone, allergens, hyperoxia). Together these properties suggest that administration of rhCC10 may help to facilitate development of normal airway epithelia and prevent the inflammation that leads to CRM in these infants.

开始日期2000-01-01

申办/合作机构

Therabron Therapeutics, Inc.

[+1]

100 项与 CC10 相关的临床结果

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100 项与 CC10 相关的转化医学

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0 项与 CC10 相关的专利（医药）

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1,684

项与 CC10 相关的文献（医药）

2025-06-01·Respiratory Medicine

Nicotine in E-cigarette aerosol may lead to pulmonary inflammation

Article

作者: Bosson, Jenny A ; Mobarrez, Fariborz ; Lyytinen, Gustaf ; Antoniewicz, Lukasz ; Hedman, Linnea ; Kabéle, Mikael ; Lundbäck, Magnus

BACKGROUNDCigarette smoking stands as one of the leading causes of preventable death globally. Alternative tobacco products, such as e-cigarettes, have gained popularity due to the general perception of being less harmful. However, much is still unknown about the health implications of these novel products. In this study, we aimed to investigate if e-cigarettes could induce pulmonary inflammatory responses by measuring lung-related circulating extracellular vesicles (EVs) in the blood of healthy volunteers following brief e-cigarette vaping sessions, with and without nicotine.METHODS22 healthy volunteers were included. Employing a randomized, double-blind, cross-over design all participants vaped 30 puffs of e-cigarette aerosol, with and without nicotine, over a 30-min period. Blood samples were collected at baseline, 30- and 105-min following exposure. Lung-related EVs were quantified using flow cytometry. Analyzed markers included angiotensin converting enzyme (ACE), aldehyde dehydrogenase 3B1 (ALDH3B1), palate, lung and epithelial clone (PLUNC), complement component 3 (C3), C-C motif chemokine ligand 3 (CCL3), also known as macrophage inflammatory protein 1 alpha (MIP-1α), and uteroglobin, also known as club cell protein 16 (CC16). All these markers are associated with pulmonary inflammation.RESULTSE-cigarette use, with nicotine but not without, resulted in a significant increase in three out of the six lung-related inflammatory markers measured and clear increases though not statistically significant in the remaining three.CONCLUSIONThe observed increase in levels of circulating lung-related inflammatory EV markers following vaping e-cigarette aerosol containing nicotine suggests that inhaled nicotine plays a central role in triggering pulmonary inflammation.CLINICALTRIALSgov ID: NCT04175457.

2025-05-01·Environmental Geochemistry and Health

Associations between air pollution and biomarkers of oxidative stress and lung damage in a large population-based sample of non-smoking adults in northern France

Article

作者: Amouyel, Philippe ; Matran, Regis ; Dauchet, Luc ; Grare, Céline ; Zerimech, Farid ; Muntaner, Manon ; Lo Guidice, Jean-Marc ; Bentegeac, Raphaël ; Achour, Djamal ; Gauthier, Victoria

AbstractAir pollution is an environmental risk factor associated with lung and cardiovascular disease that may be mediated by physiological pathways such as oxidative stress. Previous studies have identified associations between air pollution and biomarkers of oxidative stress (8-OHdG, 4-HNE, and fluorescent oxidation products (FOPs)), as well as lung health marker CC16, in younger and asthmatic populations. The objective of this study of a large population-based sample of non-smoking adults was to explore the relationship between long-term and short-term atmospheric pollution exposures and plasma or urine levels of these biomarkers. Our study was a post-hoc analysis of the cross-sectional ELISABET study from 2011 to 2013. We included non-smoking inhabitants of Lille, France from the ELISABET study. We assessed mean pluri-annual residential and short-term exposures to atmospheric pollution components (PM10, NO2, and O3) and collected several biomarkers (CC16, 8-OHdG, 4-HNE, and fluorescent oxidation products (FOPs)). We searched for associations between pollutants and biomarkers using log-linear robust multivariate regressions. Our work did not show any association between short- or long-term exposure to air pollution components and CC16, 8-OHdG, 4-HNE or FOP in a large (980 subjects) sample of Lille’s general population, despite having sufficient statistical power to replicate previous findings of associations between air pollution and these biomarkers found in younger or asthmatic populations.

2025-05-01·International Immunopharmacology

Edaravone alleviates Pseudomonas aeruginosa associated-acute lung injury by inhibiting inflammation and promoting anti-microbial peptide production

Article

作者: Song, Yuanlin ; Xu, Jian ; Wang, Jian ; Song, Juan ; Li, Yufan ; Chen, Cuicui ; Tong, Lin ; Zeng, Yingying

Acute respiratory distress syndrome (ARDS) is the most common respiratory emergency and one of the most severe clinical syndromes. Bacterial and viral infections are the frequent etiological factors. Pseudomonas aeruginosa (PA) is the most significant gram-negative pathogen associated with pneumonia and ARDS in critically ill patients with respiratory diseases. However, multi-drug resistance and biofilm formation pose significant challenges to the clinical treatment of PA-associated pulmonary infections. In this study, we focused on edaravone (EDA), a brain-protective agent and free-radical scavenger commonly used in neurology, and examined its role in PA-ALI. We found EDA significantly mitigated pulmonary pathological damage, inflammatory responses and Reactive Oxygen Species (ROS) generation induced by PA in vivo. The in-vitro assays revealed EDA inhibited the transcription and secretion of pro-inflammatory factors induced by PA in RAW264.7 cells by targeting the TLR4/MyD88/NF-κB signaling pathways. Additionally, EDA reduced the production of intracellular ROS and cell death. EDA treatment enhanced the transcription of antimicrobial peptides, including defensin beta 1 (Defb1), defensin beta 2 (Defb2), CC motif chemokine ligand 20 (Ccl20), secretory leukocyte peptidase inhibitor (Slpi), and lactotransferrin (Ltf), with a significant upregulation of Defb1 expression. We also explored the role of EDA in lung endogenous stem cells using Sftpc-DreER; Scgb1a1-CreER; R26-TLR mice. Our findings indicated that EDA promoted the regeneration of club cells in response to PA stimulation by promoting their proliferation. And also, EDA inhibited PA infection induced cell apoptosis in lung tissues. In conclusion, EDA acts as a protective agent in PA-ALI. It not only inhibits inflammatory responses induced by PA but also enhances the expression of antimicrobial peptides and promotes club cell regeneration. Therefore, EDA may serve as an adjunctive treatment for PA-ARDS.

项与 CC10 相关的新闻（医药）

2024-04-05

·生物探索

Cell | 澄清争议！周斌团队发现成体肺泡干细胞的再生起源

引言肺泡2型(AT2)细胞是肺泡上皮的干细胞。先前的遗传谱系追踪研究报道了损伤后AT2细胞的多个细胞起源。然而，传统的基于Cre-loxP的谱系追踪存在非特异性标记的局限性。2024年4月4日，国科大杭州高等研究院/中国科学院分子细胞科学卓越创新中心周斌团队在Cell 在线发表题为“Tracing the origin of alveolar stem cells in lung repair and regeneration”的研究论文，该研究引入了一种双重组酶介导的交叉遗传谱系追踪方法，能够在肺稳态、损伤和修复过程中精确研究AT2细胞的起源。该研究发现AT1细胞处于终末分化状态，在肺损伤和修复后不向AT2细胞分化。club细胞、细支气管肺泡干细胞(BASCs)和现有的AT2细胞的独特而同时的标记揭示了它们在损伤后对AT2细胞的确切贡献。在机制上，Notch信号抑制促进BASCs，但在肺修复过程中损害club细胞产生AT2细胞的能力。这种交叉遗传谱系追踪策略具有更高的精度，使得能够阐明各种上皮细胞类型在损伤后肺泡再生中的生理作用。维持肺泡结构和功能的完整性对于肺的正常稳态和功能至关重要在结构上，肺上皮由气管、细支气管和肺泡区组成。肺上皮干细胞/祖细胞参与肺稳态的分子机制的鉴定为肺损伤后的修复和再生提供了宝贵的见解。不同类型的干细胞/祖细胞存在于其局部上皮结构中，对肺损伤后的维持和修复至关重要。club细胞和神经内分泌细胞已被确定为细支气管驻地祖细胞，参与损伤后细支气管再生。肺泡区由肺泡1型(AT1)细胞和AT2细胞组成，前者负责气体交换，后者被认为是在稳态和损伤后能够自我更新并分化为AT1细胞的干细胞。此外，据报道，在细支气管肺泡-导管交界处存在一种称为细支气管肺泡干细胞(BASCs)的多能干细胞群，它们参与肺损伤后细支气管和肺泡上皮的修复。最近的多项谱系追踪研究提出了一种新的模型，即AT1细胞也可以作为各种肺泡损伤后肺泡上皮再生的细胞来源。Jain等人使用Hopx-CreER工具报道，在肺切除术(PNX)损伤后的肺中，Hopx+ AT1细胞约占AT2细胞的9%。此外，在高氧诱导的肺损伤过程中，成人和新生儿肺中再生的AT2细胞中，Hopx+ AT1细胞分别占10%和30%。这一关键工具也被用于最近的一项研究，该研究表明，分化的AT1细胞中KRAS(G12D)的表达将它们缓慢且异步地重新编程为AT2干细胞，而AT2干细胞反过来继续产生惰性肿瘤。虽然Hopx基因在胚胎(E)第13.5天左右指定AT1祖细胞，但Hopx+ Sftpc+双电位祖细胞在产前和产后阶段继续存在。谱系追踪研究进一步表明，这些双电位祖细胞在肺泡发育过程中可以分化为AT1和AT2细胞。值得注意的是，有一组AT2细胞被Hopx-CreER工具意外标记。因此，重新评估Hopx-CreER工具的特异性以及阐明AT1细胞在肺修复和肿瘤进展过程中的确切命运至关重要。模式图（Credit: Cell）除了AT1细胞外，Scgb1a1+club细胞也被报道为博莱霉素诱导的肺损伤后再生AT2细胞的祖细胞。通过单细胞RNA测序(scRNA-seq)鉴定的club细胞的H2-K1high (MHC-I+)亚群，被认为是再生AT2细胞的主要祖细胞。此外，使用Scgb1a1-CreER工具对club细胞进行遗传追踪表明，club细胞可以迁移出细支气管区域，并在博来霉素损伤后再生肺泡上皮。然而，由于体外移植和体内非特异性遗传追踪的局限性，争议仍然存在。先前的研究对Scgb1a1-CreER的非特异性标记提出了担忧，Scgb1a1-CreER除了对club细胞外，还对AT2细胞和BASCs的一个亚群进行了异位标记考虑到AT2细胞和BASCs是损伤后新AT2细胞的祖细胞，Scgb1a1-CreER工具的非特异性标记可能强烈干扰club细胞命运的解释。因此，关于AT1细胞和club细胞在肺修复和再生过程中对AT2细胞的确切作用存在争议，需要替代的遗传策略来特异性地同时针对这些不同的细胞群。该研究开发了双重组酶介导的交叉遗传策略，并对肺修复和再生过程中AT2细胞的细胞起源进行了全面的研究。交叉遗传谱系追踪结果揭示了肺泡修复过程中AT2细胞更新的起源和机制，为肺再生和潜在的疾病治疗提供了新的见解。该研究报道的新策略可广泛用于研究组织发育、再生和许多其他情况下的不同细胞起源和细胞命运。原文链接https://www-cell-com.libproxy1.nus.edu.sg/cell/fulltext/S0092-8674(24)00302-7责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

临床2期

2023-10-16

·生物谷

百草枯损伤肺上皮再生程序

NIBS/清华大学汤楠及浙江大学/南京医科大学陈静瑜共同通讯在Cell Discovery（IF=34）在线发表题为“Aberrant differentiation of epithel 组织学分析显示，百草枯毒性严重破坏了肺泡结构。在百草枯损伤的肺中，PDPN+肺泡1型(AT1)上皮细胞缺失，而proSPC+肺泡2型(AT2)上皮细胞显著减少。相反，这些区域充满α-SMA+肌成纤维细胞。存活的proSPC+ AT2细胞主要聚集在百草破损伤肺的周围，少数分散在远端气道周围。为了研究严重损伤肺的修复程序，作者进行了单细胞RNA测序(scRNA-seq)分析。共获得了19,171个转录组的全面收集，这些转录组被注释为四种广泛的细胞类型组：EPCAM+上皮细胞(n = 4120)， DCN+基质细胞(n = 2491)， PTPRC+免疫细胞(n = 10,431)和CDH5+内皮细胞(n = 2129)。基于典型谱系标记和个体细胞类型的不同分子特征，在百草枯损伤的肺中共鉴定出45种细胞类型/状态。 EPCAM+上皮细胞的无偏聚类分析揭示了十个不同的亚群。与免疫染色结果一致，没有PDPN+ AT1细胞群，表明百草枯损伤肺中完全失去了气体交换单位。这10个亚群包括SFTPC+ AT2细胞和气道上皮细胞的9个亚群，后者包括7种经典定义的细胞类型(基底细胞、MUC5AChigh杯状细胞、SAAhigh杯状细胞、scgb1a11low杯状细胞、棒状细胞、纤毛细胞和肺神经内分泌细胞)和两种中间状态(分化基底细胞和分化棒状细胞)。分化的基底细胞同时表达基底细胞标记物(KRT5和KRT15)和杯状细胞标记物(SERPINB3、SERPINB4和CLCA2) ，表明它们是杯状细胞的祖细胞。新鉴定的分化俱乐部细胞表达俱乐部细胞(SCGB3A2和SCGB1A1)和杯状细胞(MUC5B)的标记物。鉴于杯状细胞被认为是终末分化的细胞类型，正在分化的俱乐部细胞可能代表俱乐部细胞向杯状细胞分化的中间阶段。百草枯损伤的人肺异常上皮修复程序（图源自Cell Discovery ）在健康供肺中，EPCAM+上皮细胞包括肺泡上皮细胞(AT1和AT2细胞)和气道上皮细胞，肺泡上皮细胞占EPCAM+细胞总数的40%以上。然而，在百草枯损伤的肺中，肺泡上皮细胞（AT2细胞群）的比例显著下降至9.4%，而气道上皮细胞的比例则增加到90.6%。具体而言，气道干/祖细胞的比例，包括基底细胞(27.4%)、俱乐部细胞(17.5%)、分化基底细胞(7.4%)和分化俱乐部细胞(4.7%)，显著增加。这些发现表明，百草枯损伤的肺经历了积极的气道修复程序，但肺泡修复程序不充分。研究分析显示，基底细胞具有更高的分化基底细胞的倾向。俱乐部细胞可以通过分化的俱乐部细胞分化为杯状细胞，这支持了俱乐部细胞分化为杯状细胞的中间阶段的观点。先前利用小鼠肺损伤模型的研究表明，气道祖细胞可以分化为AT2和AT1细胞。然而，分析显示，在百草枯损伤的肺中，基底细胞、分化的基底细胞和俱乐部细胞分化为AT2细胞的概率有限。相反，在百草枯损伤的肺中，AT2细胞表现出更高的分化为俱乐部细胞的倾向。综上所述，这些结果表明，副损伤肺中的AT2细胞和气道干/祖细胞再生肺泡上皮的能力显著降低，最终导致气体交换单位的不可逆转损失。该研究通过实验证明，百草枯损伤肺上皮再生程序。百草枯中毒后大量细胞死亡，导致免疫细胞显著浸润，气体交换单元丧失，肺纤维化，导致肺组织广泛缺氧微环境。这种微环境可能通过激活NOTCH信号和破坏气道和肺泡干细胞/祖细胞的分化来促进异常修复程序，从而加剧肺组织损伤。该研究结果表明，肺移植可能是严重百草枯中毒患者唯一可行的治疗方法。重要的是，作者研究强调了适当的微环境在再生功能肺泡单位中的关键作用，这取决于新形成的AT1细胞的分化。由于缺氧是严重肺部疾病的共同特征，未来针对缺氧肺微环境的治疗策略，如减少缺氧或抑制NOTCH信号，可能有望治疗严重肺损伤。

临床结果