气管移植术后手术应激相关蛋白质组学分析凸显基质细胞外基质改变

Proteomic Analysis of Surgery-induced Stress Post-Tracheal Transplantation Highlights Changes in Matrisome.

机构信息

Department of Otolaryngology, Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

出版信息

Laryngoscope. 2024 Sep;134(9):4052-4059. doi: 10.1002/lary.31501. Epub 2024 May 14.

DOI:10.1002/lary.31501

PMID:38742543

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11305956/

Abstract

OBJECTIVE

Investigate the impact of Surgery-induced stress (SIS) on the normal airway repair process after airway reconstruction using a mouse microsurgery model, mass spectrometry (MS), and bioinformatic analysis.

METHODS

Tracheal tissue from non-surgical (N = 3) and syngeneic tracheal grafts at 3 months post-replacement (N = 3) were assessed using mass spectrometry. Statistical analysis was done using MASCOT via Proteome Discoverer™. Proteins were categorized into total, dysregulated, suppressed, and evoked proteins in response to SIS. Dysregulated proteins were identified using cut-off values of -1 1 and t-test (p value <0.05). Enriched pathways were determined using STRING and Metascape.

RESULTS

At the three-month post-operation mark, we noted a significant increase in submucosal cellular infiltration (14343 ± 1286 cells/mm, p = 0.0003), despite reduced overall thickness (30 ± 3 μm, p = 0.01), compared to Native (4578 ± 723 cells/mm; 42 ± 6 μm). Matrisome composition remained preserved, with proteomic analysis identifying 193 commonly abundant proteins, encompassing 7.2% collagens, 34.2% Extracellular matrix (ECM) glycoproteins, 6.2% proteoglycans, 33.2% ECM regulators, 14.5% Extracellular matrix-affiliated, and 4.7% secreted factors. Additionally, our analysis unveiled a unique proteomic signature of 217 "Surgery-evoked proteins" associated with SIS, revealing intricate connections among neutrophils, ECM remodeling, and vascularization through matrix metalloproteinase-9 interaction.

CONCLUSIONS

Our study demonstrated the impact of SIS on the extracellular matrix, particularly MMP9, after airway reconstruction. The novel identification of MMP9 prompts further investigation into its potential role in repair.

LEVEL OF EVIDENCE

NA Laryngoscope, 134:4052-4059, 2024.

摘要

目的

利用小鼠显微手术模型、质谱（MS）和生物信息学分析，研究手术引起的应激（SIS）对气道重建后正常气道修复过程的影响。

方法

使用质谱法评估非手术（N=3）和同种异体气管移植物在替换后 3 个月（N=3）的气管组织。通过 Proteome Discoverer™ 使用 MASCOT 进行统计分析。将蛋白质分为总蛋白、失调蛋白、受抑蛋白和 SIS 诱导蛋白。使用 -1 1 和 t 检验（p 值<0.05）的截止值识别失调蛋白。使用 STRING 和 Metascape 确定富集途径。

结果

在术后 3 个月标记时，与 Native（4578±723 个细胞/mm；42±6μm）相比，我们注意到黏膜下细胞浸润显著增加（14343±1286 个细胞/mm，p=0.0003），尽管总体厚度减少（30±3μm，p=0.01）。基质组组成保持不变，蛋白质组分析鉴定出 193 种常见丰富蛋白，包含 7.2%的胶原蛋白、34.2%的细胞外基质（ECM）糖蛋白、6.2%的蛋白聚糖、33.2%的 ECM 调节剂、14.5%的细胞外基质相关蛋白和 4.7%的分泌因子。此外，我们的分析还揭示了 217 种“手术诱导蛋白”的独特蛋白质组学特征，这些蛋白与 SIS 相关，通过基质金属蛋白酶-9 相互作用揭示了中性粒细胞、ECM 重塑和血管生成之间的复杂联系。