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3月8日下调调节了包括肌纤维细胞分化在内的亲纤维细胞反应

Xia Guo¹, Oluwaseun Adeyanju¹, Ayobami Matthew Olajuyin¹

¹Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, United States.

American journal of physiology. Cell physiology

|September 4, 2023

概括

膜相关的RING-CH 8 (MARCH8) 表达在异常性肺纤维化 (IPF) 中降低. 抑制MARCH8抑制纤维细胞转变为肌纤维细胞,这表明MARCH8是IPF的潜在治疗标.

科学领域:

肺部医学肺部医学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

间歇性肺部疾病 (ILD),特别是异常性肺纤维化 (IPF),由于治疗选择有限,患者的治疗结果不佳.
了解驱动纤维化病理机制对于开发新疗法至关重要.
膜相关RING-CH 8 (MARCH8) 在肺纤维化和纤维细胞激活中的作用在很大程度上是未知的.

研究的目的:

为了调查MARCH8在肺纤维化病原体中的作用.
确定转化生长因子-β (TGF-β) 对人类肺纤维细胞 (HLFs) MARCH8表达和功能的影响.
探索MARCH8作为IPF的潜在治疗点.

主要方法:

在IPF患者和对照患者的MARCH8表达的比较,以及在白血素诱导的肺纤维化模型中.
用TGF-β治疗正常和IPF的HLF,以评估MARCH8和纤维细胞向肌纤维细胞过渡 (FMT) 标记物的变化 (α-SMA,I型原蛋白,纤维素).
在HLF中利用MARCH8过度表达和siRNA淘汰来评估其对TGF-β诱导的FMT和Smad2/3酸化的调节效应.

主要成果:

在IPF肺部和白血素诱导纤维化模型中,MARCH8表达显著下降.
TGF-β以剂量和时间依赖的方式降低了HLFs中的MARCH8表达,与增加的FMT标志物相关.
MARCH8的过度表达抑制了TGF-β诱导的FMT,而MARCH8的淘汰则增强了基底和TGF-β诱导的FMT标记表达.
在MARCH8中,TGF-β诱导的下降发生在转录水平上,并与减少的Smad2/3酸化有关.

结论:

MARCH8作为纤维细胞向肌纤维细胞过渡 (FMT) 的负调节剂.
对MARCH8的降低调节与IPF观察到的益纤维素反应有关.
3月8日代表了治疗肺纤维化的一种新型治疗标.

关键词:

在IPF中,IPF是IPF.3月8日时间:在TGF-β的基础上.纤维细胞细胞是什么?肺肺肺肺肺肺肺肺肺

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