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转化生长因子的机制-β1诱导纤维化,基于转录组测序分析

Huanan Li¹, Peifen Li², Shanyi Li²

¹Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China. hnli@yzu.edu.cn.

Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences

|November 2, 2023

概括

转化生长因子-β1 (TGF-β1) 诱导细胞基因表达的变化,突出了Irf8和Myc作为治疗纤维化和慢性病的潜在标.

科学领域:

腎臟病學 (nephrology) 是一種醫學.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

纤维化是慢性病 (CKD) 中的一个关键病理过程.
转化生长因子-β1 (TGF-β1) 是纤维化发展的关键媒介.
了解TGF-β1诱导纤维化背后的分子机制对于开发向疗法至关重要.

研究的目的:

阐明TGF-β1诱导纤维化的分子机制.
确定参与TGF-β1介导纤维细胞激活的关键基因和信号通路.
为了验证纤维化的潜在治疗标.

主要方法:

进行RNA测序 (RNA-seq) 在用TGF-β1.1治疗的纤维细胞NRK-49F细胞上.
使用DESeq2.2进行了差异基因表达分析.
进行了基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG) 路径丰富分析.
关键转录因子的验证在细胞模型,单边尿路阻塞 (UUO) 诱导的小鼠纤维化模型和公共基因表达数据集 (GSE104954) 中进行.

主要成果:

TGF-β1治疗诱导了纤维细胞中数百个基因的显著差异性表达.
富化分析揭示了Hippo,TGF-β和Wnt信号通路的改变,以及细胞外矩阵相互作用.
验证发现Irf8和Myc在纤维化细胞和动物模型中显著上调,IRF8和MYC在人类病数据集中也显示出改变的表达.

结论:

TGF-β1在纤维细胞中诱导复杂的转录反应,导致纤维化.
已确定Irf8和Myc是TGF-β1诱导纤维化中的关键转录因子.
在治疗慢性病和纤维化方面,Irf8和Myc是潜在的治疗点.

关键词:

纤维细胞细胞.机理机制机理机制我们的老鼠是老鼠.患有脏纤维化转录组转录组就是一个转录组.转化生长因子-β1的转化.

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TGF - β Signaling Pathway

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