HMGB1,KSHV感染内皮细胞中瘤微环境的潜在调节者
Myung-Ju Lee1, Joohee Park1, Seokjoo Choi1
1Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, Republic of Korea.
Frontiers in microbiology
|July 31, 2023
概括
高流动性组盒1 (HMGB1) 蛋白质通过调节细胞因子分泌促进卡波西肉瘤 (KS) 的发展. 它的缺失降低了KSHV感染细胞的活力,这表明HMGB1是潜在的KS治疗标.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 高流动性组盒1 (HMGB1) 是一种参与细胞过程和癌症进展的DNA结合蛋白.
- 尚不清楚HMGB1在卡波西肉瘤 (KS) 发病过程中的作用及其与卡波西肉瘤相关的人类疹病毒 (KSHV) 的相互作用.
- HMGB1影响瘤微环境,促进瘤生长和免疫逃避.
研究的目的:
- 研究HMGB1在卡波西肉瘤 (KS) 病变发生中的作用.
- 为了确定HMGB1对KSHV感染的人体内皮细胞的影响.
- 探索HMGB1作为KS的潜在治疗点.
主要方法:
- 使用了被KSHV感染的人类内皮细胞.
- 通过使用CRISPR/Cas9.9生成HMGB1淘汰 (KO) 细胞系.
- 在二维和三维培养中分析了细胞活力,并通过抗体阵列测量了细胞因子/生长因子分泌.
主要成果:
- 在人类内皮细胞中,KSHV感染诱导HMGB1分泌.
- 在KSHV感染细胞中缺少HMGB1会降低细胞活力,但不会诱导细胞复制.
- 在HMGB1 KO KSHV感染细胞中抑制了CXCL5,PDGF-AA,G-CSF,Emmprin,IL-17A和VEGF的分泌.
- p38酸化与CXCL5,PDGF-A和VEGF的转录调节有关.
结论:
- 通过调节细胞因子和生长因子分泌,HMGB1在KS病变发生过程中发挥着关键作用.
- HMGB1影响KSHV感染的内皮细胞活力.
- 调节HMGB1可能是通过向瘤微环境来针对KS的潜在治疗策略.
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