目的 本研究揭示骨膜蛋白（Periostin，POSTEN）在瘢痕疙瘩形成过程中的作用机制及其对活化B细胞核因子κ轻链增强子（Nuclear Factor kappa-light-chain-enhancer of activated B cells, NFκB）信号通路、内质网应激（Endoplasmic reticulum stress, ER Stress）调控及细胞增殖行为影响。 方法 利用GSE44270数据集和Genecards数据库进行Venn分析及STRING/Cytoscape蛋白互作网络构建。采用Western blot、qRT-PCR检测POSTEN表达；免疫荧光观察定位；Transwell和EdU实验评估迁移和增殖；Western blot检测NFκB通路关键蛋白（p-NFκB）及内质网应激标志物（GRP78, CHOP）。 结果 与人皮肤成纤维细胞（Normal human dermal fibroblasts, NF）相比，人瘢痕疙瘩成纤维细胞（Human keloid fibroblasts, KF）中POSTEN蛋白及mRNA表达水平显著上升（P<0.05）。敲低POSTEN后，POSTEN表达显著下降（P<0.05），伴随EdU阳性细胞率、迁移侵袭细胞数显著减少（P<0.05），同时p-NFκB、GRP78和CHOP蛋白水平也显著降低（P<0.05）。 结论 POSTEN 在瘢痕疙瘩成纤维细胞中高表达，可通过激活 NFκB 信号通路诱发内质网应激，进而促进瘢痕疙瘩成纤维细胞增殖、迁移与侵袭，最终推动瘢痕疙瘩形成；靶向抑制 POSTEN 可能成为瘢痕疙瘩治疗的潜在策略。
Abstract
Objective To reveal the mechanism of periostin (POSTEN) in the formation of keloids and its influence on the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling pathway, endoplasmic reticulum stress (ER Stress) regulation, and cell proliferation behavior. Methods Venn analysis and STRING/Cytoscape protein interaction network construction were performed using the GSE44270 dataset and Genecards database. Western blot and qRT-PCR were used to detect POSTEN expression. Immunofluorescence was used for localization. Transwell and EdU assays were used to evaluate migration and proliferation. Western blot was used to detect the levels of key proteins in the NFκB pathway (p-NFκB) and endoplasmic reticulum stress markers (GRP78, CHOP). Results Compared with normal human dermal fibroblasts (NF), the expression levels of POSTEN protein and mRNA in human keloid fibroblasts (KF) were significantly increased (P<0.05). After POSTEN knockdown, POSTEN expression was significantly decreased (P<0.05), accompanied by a significant reduction in EdU positive cell rate and the number of migrating and invasive cells (P<0.05), and the levels of p-NFκB, GRP78, and CHOP proteins were also significantly decreased (P<0.05). Conclusions POSTEN is highly expressed in keloid fibroblasts. It can induce endoplasmic reticulum stress by activating the NFκB signaling pathway, thereby promoting the proliferation, migration and invasion of keloid fibroblasts, and ultimately facilitating the formation of keloids; Targeted inhibition of POSTEN may become a potential strategy for the treatment of keloids.
关键词
瘢痕疙瘩 /
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POSTEN /
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增殖 /
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内质网应激 /
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NFκB
Key words
Keloid /
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POSTEN /
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Proliferation /
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Endoplasmic reticulum stress /
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NFκB
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基金
河南省医学科技公关计划联合共建项目（LHGJ20220673）
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