Quantitative proteomics approach reveals novel biomarkers and pathological mechanism of keloid.
Quantitative proteomics approach reveals novel biomarkers and pathological mechanism of keloid.
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DOI：
10.1002/prca.202100127
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发表时间：
2022-07
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瘢痕疙瘩是一种具有复杂分子病理机制的病理性皮肤瘢痕形成。需要新的生物标记物和相关机制来改进目前的治疗方法。目的：确定瘢痕疙瘩新的生物标志物和潜在的病理机制。采用基于高分辨率无标记质谱仪的蛋白质组学方法，对6对瘢痕疙瘩瘢痕组织和相应的正常皮肤组织进行了定量分析。通过综合生物信息学方法进一步分析差异蛋白质表达数据，以确定瘢痕疙瘩形成的新生物标志物和机制途径。对候选生物标志物进行了实验验证。通过蛋白质组学分析，共鉴定出1359个蛋白质。其中206种蛋白在瘢痕疙瘩组织和正常皮肤组织中的表达存在显著差异。RCN3和CALU在瘢痕疙瘩中显著上调。RCN1和PDGFRL仅在瘢痕疙瘩中表达。通路分析表明，XBP1介导的未折叠蛋白反应(UPR)通路参与了瘢痕疙瘩的形成。此外，构建了以PDGFRL为中心的基因共表达网络，以阐明其在皮肤中的功能。我们的研究提出了四个新的生物标志物，并强调了XBP1介导的UPR通路在瘢痕疙瘩病理中的作用。它提供了新的生物学见解，有助于开发治疗瘢痕疙瘩的新策略。
Keloid is a pathological skin scar formation with complex and unclear molecular pathology mechanism. Novel biomarkers and associated mechanisms are needed to improve current therapies. To identify novel biomarkers and underlying pathological mechanisms of keloids. Six pairs of keloid scar tissues and corresponding normal skin tissues were quantitatively analyzed by a high‐resolution label‐free mass spectrometry‐based proteomics approach. Differential protein expression data was further analyzed by a comprehensive bioinformatics approach to identify novel biomarkers and mechanistic pathways for keloid formation. Candidate biomarkers were validated experimentally. In total, 1359 proteins were identified by proteomic analysis. Of these, 206 proteins exhibited a significant difference in expression between keloid scar and normal skin tissues. RCN3 and CALU were significantly upregulated in keloids. RCN1 and PDGFRL were uniquely expressed in keloids. Pathway analysis suggested that the XBP1‐mediated unfolded protein response (UPR) pathway was involved in keloid formation. Moreover, a PDGFRL centric gene coexpression network was constructed to illustrate its function in skin. Our study proposed four novel biomarkers and highlighted the role of XBP1‐mediated UPR pathway in the pathology of keloids. It provided novel biological insights that contribute to develop novel therapeutic strategies for keloids.