皮肤桥蛋白通过IL-1β-COL1A1轴促进腹主动脉瘤发展

doi:10.16352/j.issn.1001-6325.2025.07.0918

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (7): 918-925.doi: 10.16352/j.issn.1001-6325.2025.07.0918

皮肤桥蛋白通过IL-1β-COL1A1轴促进腹主动脉瘤发展

印华润^1#, 赵宁^2#, 吴志远², 李拥军^2*, 尹洪超^1*

1.中国医学科学院基础医学研究所北京协和医学院基础学院病理生理学系,北京 100005;
2.北京医院血管外科国家老年医学中心中国医学科学院老年医学研究院,北京 100730

收稿日期:2025-04-07 修回日期:2025-05-20 出版日期:2025-07-05 发布日期:2025-06-24
通讯作者: ^*liyongjun4679@bjhmoh.cn;yinhc@ibms.pumc.edu.cn
作者简介:^#对本文有相同贡献
基金资助:
西藏自治区科技计划(XZ202501ZY0115);中央高水平医院临床科研业务费(BJ-2024-142,BJ-2021-205)

Dermatopontin promotes abdominal aortic aneurysm progression via the IL-1β-COL1A1 axis

YIN Huarun^1#, ZHAO Ning^2#, WU Zhiyuan², LI Yongjun^2*, YIN Hongchao^1*

1. Department of Pathophysiology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. Department of Vascular Surgery, Beijing Hospital, National Center for Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

Received:2025-04-07 Revised:2025-05-20 Online:2025-07-05 Published:2025-06-24
Contact: ^*liyongjun4679@bjhmoh.cn;yinhc@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探讨皮肤桥蛋白(DPT)在腹主动脉瘤(AAA)的表达情况和促进其进展的机制。方法使用差异基因表达(DEG)分析、GO-KEGG基因通路富集分析DPT在AAA中表达量和相关通路。选取于北京医院进行开放性手术修复的AAA患者为实验组(n=3),对照组腹主动脉来自肾移植供体(n=3)。免疫组织化学和免疫荧光染色验证AAA组织的DPT蛋白表达差异。用Masson染色评估各组纤维化程度。人主动脉平滑肌细胞(HASMCs)分为对照(Ctrl)组和人源脂多糖(LPS)干预组(n=3),使用RT-qPCR、ELISA和免疫细胞化学(ICC)方法检测各组间DPT表达量。HASMCs分为对照(Ctrl)组和人源重组皮肤桥蛋白(DPT)干预组(n=3),使用RT-qPCR检测白细胞介素-1α基因 IL-1α、白细胞介素基因 IL-1β、Ⅰ型胶原蛋白α1链基因CoL1A1、基质金属蛋白酶-2基因MMP2和基质金属蛋白酶-9基因MMP9的表达。细胞黏附实验检测整合素α3和整合素β1对HASMCs粘附作用。结果 DPT在人AAA组织中高表达(P＜0.01)。LPS可诱导HASMCs中DPT的表达和分泌(P＜0.05)。DPT通过正反馈促进IL-1α(P＜0.001)/IL-1β(P＜0.01)表达,同时抑制COL1A1(P＜0.001)生成。DPT通过整合素α3β1受体增强HASMCs黏附能力(P＜0.001)。结论 DPT通过激活IL-1α/IL-1β炎性因子,并抑制COL1A1介导细胞外基质(ECM)重塑,从而促进AAA发展,整合素α3β1可能参与其调控。

关键词: 腹主动脉瘤, 皮肤桥蛋白, 炎性反应, 细胞外基质重塑, 平滑肌细胞

Abstract: Objective To investigate the expression of dermatopontin (DPT) in abdominal aortic aneurysm (AAA) and to explore the mechanism in promoting AAA progression. Methods Differential gene expression (DEG) and GO-KEGG pathway enrichment were used to assess DPT expression level and related pathways in AAA. AAA tissue samples were collected from patients undergoing open surgical repair at Beijing Hospital (experimental group, n=3), while control aortic tissues were collected from kidney transplant donors (n=3). Immun-ohistochemistry and immuno-fluorescence staining were performed to validate DPT protein expression differences in AAA tissues. Masson staining microscopy was used to evaluate fibrosis level. Human aortic smooth muscle cells (HASMCs) were divided into control (Ctrl) and lipopolysaccharide (LPS)-treated groups (n=3). RT-qPCR, ELISA, and immunocytochemistry (ICC) were used to measure DPT expression level. HASMCs were further divided into control (Ctrl) and recombinant human DPT-treated groups with 3 cases in each. RT-qPCR was performed to detect the expression of interleukin-1α (IL-1α), interleukin-1β(IL-1β), collagen type Ⅰ alpha 1 chain (COL1A1), matrix metalloproteinase-2(MMP2), and matrix metalloproteinase-9(MMP9). Cell adhesion assays were conducted to examine the role of integrin α3 and integrin β1 in HASMC adhesion. Results DPT was highly expressed in human AAA tissues (P＜0.01). LPS induced DPT expression and secretion in HASMCs (P＜0.05). DPT promoted IL-1α (P＜0.001) and IL-1β (P＜0.01) expression through a positive feedback mechanism while suppressed COL1A1 (P＜0.001) production. DPT enhanced HASMC adhesion via the integrin α3β1 receptor (P＜0.001). Conclusions DPT promotes AAA progression by activating IL-1α/IL-1β inflammatory cytokines and inhibits COL1A1-mediated extra cellular matrix (ECM) remodeling.Integrin α3β1 is potentially involved in the regulation process.

Key words: abdominal aortic aneurysm, dermatopontin, inflammatory response, extracellular matrix remodeling, smooth muscle cell

中图分类号:

R543.16

印华润, 赵宁, 吴志远, 李拥军, 尹洪超. 皮肤桥蛋白通过IL-1β-COL1A1轴促进腹主动脉瘤发展[J]. 基础医学与临床, 2025, 45(7): 918-925.

YIN Huarun, ZHAO Ning, WU Zhiyuan, LI Yongjun, YIN Hongchao. Dermatopontin promotes abdominal aortic aneurysm progression via the IL-1β-COL1A1 axis[J]. Basic & Clinical Medicine, 2025, 45(7): 918-925.

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皮肤桥蛋白通过IL-1β-COL1A1轴促进腹主动脉瘤发展

Dermatopontin promotes abdominal aortic aneurysm progression via the IL-1β-COL1A1 axis

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