Collagen XVIII (COL18) is a multifaceted component of the extracellular matrix, belonging to the multiplexin collagen family characterized by interrupted triple-helical domains and multiple non-collagenous regions. It exists as three major isoforms (short, medium, and long) produced by alternative splicing of the COL18A1 gene. The protein’s C-terminal end contains the endostatin domain, a bioactive fragment with anti-angiogenic properties released upon proteolytic cleavage. COL18 is widely expressed in basement membranes of tissues like the liver, kidney, and eye, where it contributes to structural stability, cell adhesion, and tissue organization.
Research on COL18 gained momentum due to its role in human diseases. Mutations in COL18A1 are linked to Knobloch syndrome, a rare disorder characterized by ocular defects and occipital encephalocele. Additionally, COL18 deficiency in mice models revealed impaired retinal angiogenesis and muscle regeneration, highlighting its importance in developmental and repair processes. The endostatin domain, in particular, has been extensively studied for its ability to inhibit endothelial cell proliferation and tumor growth, making it a candidate for anticancer therapies.
Recombinant COL18 proteins, often generated in mammalian or bacterial expression systems, enable detailed functional studies and therapeutic exploration. These proteins retain critical domains for binding heparan sulfate proteoglycans and integrins, facilitating research into their roles in vascular biology, fibrosis, and tissue remodeling. Recombinant endostatin (e.g., Endostar) has already entered clinical trials for cancers and age-related macular degeneration. Challenges remain in producing full-length COL18 with proper post-translational modifications, but advances in protein engineering continue to refine its applications in regenerative medicine and disease modeling. Overall, COL18 exemplifies the intersection of structural complexity and therapeutic potential in extracellular matrix biology. (Word count: 398)
以下是关于COL17重组蛋白的3篇参考文献，涵盖其功能、表达及医学应用：
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1. **文献名称**：*Collagen XVII promotes epidermal stem cell maintenance via regulation of hemidesmosome dynamics*
**作者**：Rieko Nishiguchi et al.
**摘要**：该研究揭示了COL17A1(胶原XVII)通过调控半桥粒稳定性维持表皮干细胞自我更新的机制。实验表明，COL17重组蛋白的缺失导致干细胞分化异常，影响皮肤再生能力。
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2. **文献名称**：*Recombinant expression of human collagen XVII in mammalian cells and structural characterization*
**作者**：Yutaka Hieda et al.
**摘要**：研究成功在哺乳动物细胞中表达并纯化功能性重组COL17蛋白，解析其跨膜结构域的关键功能，为研究大疱性皮肤病的分子机制提供工具。
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3. **文献名称**：*Autoantibody detection using recombinant collagen XVII in bullous pemphigoid diagnosis*
**作者**：Giovanni Di Zenzo et al.
**摘要**：利用重组COL17蛋白作为抗原开发高灵敏度ELISA检测法，显著提高大疱性类天疱疮患者自身抗体的诊断准确率，推动临床检测标准化。
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这些文献分别从基础机制、蛋白工程及临床诊断角度探讨了COL17重组蛋白的应用价值。
COL17 (Type XVII collagen), also known as BP180 or BPAG2. is a transmembrane protein belonging to the collagen family. It is encoded by the COL17A1 gene in humans, located on chromosome 10. Structurally, COL17 consists of a non-collagenous intracellular N-terminal domain, a transmembrane region, and a large extracellular C-terminal domain containing multiple collagenous repeats. This unique configuration allows it to anchor epithelial cells to the basement membrane by forming hemidesmosomes, critical structures for epidermal-dermal adhesion. COL17 interacts with laminin-332 and integrin α6β4. stabilizing tissue integrity in skin and mucous membranes.
Functionally, COL17 plays a vital role in maintaining epithelial homeostasis, tissue regeneration, and wound healing. Its expression is particularly prominent in basal keratinocytes. Research has linked COL17 mutations to junctional epidermolysis bullosa (JEB), a blistering skin disorder characterized by fragile skin and mucosal tissues. Additionally, COL17 dysregulation is implicated in autoimmune blistering diseases like bullous pemphigoid, where autoantibodies target its extracellular domain, disrupting cell-matrix adhesion.
Recombinant COL17 protein, typically produced in mammalian or insect cell systems, retains key functional domains and is widely used to study molecular mechanisms of skin diseases, screen therapeutic antibodies, or model cell-matrix interactions. In cancer biology, COL17 overexpression in certain carcinomas correlates with tumor invasion and metastasis, highlighting its dual role in tissue repair and pathology. Recent studies also explore its potential in regenerative medicine, as COL17 expression declines with aging, affecting stem cell maintenance. Therapeutic strategies leveraging recombinant COL17 aim to restore hemidesmosome function or block pathogenic autoantibodies, offering promising avenues for treating genetic and acquired epithelial disorders.
在生物科技领域，蛋白研发与生产是前沿探索的关键支撑。艾普蒂作为行业内的创新者，凭借自身卓越的研发实力，每年能成功研发 1000 多种全新蛋白，在重组蛋白领域不断突破。 在重组蛋白生产过程中，艾普蒂积累了丰富且成熟的经验。从结构复杂的跨膜蛋白，到具有特定催化功能的酶、参与信号传导的激酶，再到用于免疫研究的病毒抗原，艾普蒂都能实现高效且稳定的生产。 这一成就离不开艾普蒂强大的技术平台。我们构建了多元化的重组蛋白表达系统，昆虫细胞、哺乳动物细胞以及原核蛋白表达系统协同运作。不同的表达系统各有优势，能够满足不同客户对重组蛋白的活性、产量、成本等多样化的需求，从而提供高品质、低成本的活性重组蛋白。 艾普蒂提供的不只是产品，更是从源头到终端的一站式解决方案。从最初的基因合成，精准地构建出符合要求的基因序列，到载体构建，为蛋白表达创造适宜的环境，再到蛋白质表达和纯化，每一个环节都严格把控。我们充分尊重客户的个性化需求，在表达 / 纯化标签的选择、表达宿主的确定等方面，为客户量身定制专属方案。 同时，艾普蒂还配备了多种纯化体系，能够应对不同特性蛋白的纯化需求。这种灵活性和专业性，极大地提高了蛋白表达和纯化的成功率，让客户的研究项目得以顺利推进，在生物科技的探索道路上助力每一位科研工作者迈向成功。
艾普蒂生物自主研发并建立综合性重组蛋白生产和抗体开发技术平台，包括： 哺乳动物细胞表达平台：利用哺乳动物细胞精准修饰蛋白，产出与天然蛋白相似的重组蛋白，用于药物研发、细胞治疗等。 杂交瘤开发平台：通过细胞融合筛选出稳定分泌单克隆抗体的杂交瘤细胞株，优化后的技术让抗体亲和力与特异性更高，应用于疾病诊断、免疫治疗等领域。 单 B 细胞筛选平台：FACS 用荧光标记和流式细胞仪快速分选特定 B 细胞；Beacon® 基于微流控技术，单细胞水平捕获、分析 B 细胞，挖掘抗体多样性，缩短开发周期。 凭借这些平台，艾普蒂生物为客户提供优质试剂和专业 CRO 技术服务，推动生物科技发展。
艾普蒂生物在重组蛋白和天然蛋白开发领域经验十分丰富，拥有超过 2 万种重组蛋白的开发案例。在四大重组蛋白表达平台的运用上，艾普蒂生物不仅经验老到，还积累了详实的成功案例。针对客户的工业化生产需求，我们能够定制并优化实验方案。通过小试探索、工艺放大以及条件优化等环节，对重组蛋白基因序列进行优化，全面探索多种条件，精准找出最契合客户需求的生产方法。 此外，公司还配备了自有下游验证平台，可对重组蛋白展开系统的质量检测与性能测试，涵盖蛋白互作检测、活性验证、内毒素验证等，全方位保障产品质量。 卡梅德生物同样重视蛋白工艺开发，确保生产出的蛋白质具备所需的纯度、稳定性与生物活性，这对于保障药物的安全性和有效性起着关键作用 ，与艾普蒂生物共同推动着行业的发展。
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