TEM1/endosialin/CD248通过其在皮肤纤维细胞中的受体稳定性促进病理性痕和TGF-β活性
Yi-Kai Hong1,2,3,4, Yu-Chen Lin1,2, Tsung-Lin Cheng5,6,7,8,9
1Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Journal of biomedical science
|January 23, 2024
概括
瘤内皮标记1 (TEM1) 在病理性痕中升高,促进纤维细胞激活. 用ontuxizumab针对TEM1降低了 keloid 尺寸和原密度,这表明了一种新的治疗策略.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 病理性痕,如状体和过度缩性痕,很难治疗.
- 这些痕的基础生物学还不太清楚.
- TEM1 (endosialin/CD248) 是一种被研究其在痕发育中的作用的跨膜蛋白.
研究的目的:
- 研究TEM1对病理性痕发展的影响.
- 探索TEM1在纤维细胞激活和细胞外基质 (ECM) 生产中的作用.
主要方法:
- 利用免疫光学,西式涂抹和单细胞RNA测序 (scRNA-seq) 来评估TEM1的表达.
- 在体外细胞培养和体内小鼠模型中进行了伸展诱导的痕.
- 研究了TEM1在TGF-β介导反应中的参与.
主要成果:
- 与正常皮肤相比,TEM1蛋白质水平在过度缩的痕和 keloids 中较高.
- scRNA-seq显示,TEM1在profibrotic纤维细胞中高度表达,随着激活而增加.
- 通过稳定TGF-β受体,TEM1增强纤维细胞激活,增殖和ECM产生.
- 在小鼠痕模型中,Tem1的全球删除减少了ECM合成和炎症.
- 内注射的ontuxizumab (抗TEM1抗体) 显著降低了 keloid 尺寸和原密度.
结论:
- 通过增强TGF-β信号传递和激活皮肤纤维细胞,TEM1在病理性痕中发挥着重要作用.
- 准TEM1为治疗病理性痕提供了一个有前途的新疗法.
- 对TEM1机制的进一步研究可能会导致改善痕治疗.
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