METTL3通过m6A RNA甲基化GRAMD1B mRNA促进增生性瘢痕纤维化。

IF 2.2 4区 生物学 Q3 CELL BIOLOGY
Wanli Guo, Wei Song, Yanbin Zhai, Peiyi Bai, Zhihui Guo, Xiaorui Tian, Peng Duan
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引用次数: 0

摘要

增生性瘢痕形成(HS)是一种常见的纤维化疾病,其特征是细胞外基质过度沉积和成纤维细胞增殖。由METTL3介导的n6 -甲基腺苷(m6A) RNA甲基化已成为基因表达和细胞过程的关键调节因子。本研究探讨了mettl3介导的m6A甲基化在增生性瘢痕纤维化中的作用。我们发现,在人增生性瘢痕组织和TGF-β1诱导的人真皮成纤维细胞中,METTL3的表达和m6A RNA甲基化水平显著升高。沉默METTL3降低m6A甲基化,损害成纤维细胞增殖,降低纤维化标志物(ACTA2、Col1a1、Col3a1和CTGF)的mRNA和蛋白表达。生物信息学分析发现GRAMD1B是HS组织中关键的差异表达基因。mettl3介导的m6A甲基化增强了GRAMD1B mRNA的稳定性,促进了其表达。这些发现表明,METTL3通过调节GRAMD1B mRNA的m6A甲基化促进增生性瘢痕纤维化,突出了METTL3作为纤维化疾病的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
METTL3 promotes the hypertrophic scar fibrosis via m6A RNA methylation of GRAMD1B mRNA.

Hypertrophic scarring (HS) is a common fibrotic disorder characterized by excessive extracellular matrix deposition and fibroblast proliferation. N6-methyladenosine (m6A) RNA methylation, mediated by METTL3, has emerged as a critical regulator of gene expression and cellular processes. This study investigates the role of METTL3-mediated m6A methylation in hypertrophic scar fibrosis. We found that METTL3 expression and m6A RNA methylation levels were significantly elevated in human hypertrophic scar tissues and TGF-β1-induced human dermal fibroblasts. Silencing METTL3 reduced m6A methylation, impaired fibroblast proliferation, and decreased the mRNA and protein expression of fibrotic markers (ACTA2, Col1a1, Col3a1, and CTGF). Bioinformatics analysis identified GRAMD1B as a key differentially expressed gene in HS tissues. METTL3-mediated m6A methylation enhanced GRAMD1B mRNA stability, promoting its expression. These findings suggest that METTL3 contributes to hypertrophic scar fibrosis by regulating m6A methylation of GRAMD1B mRNA, highlighting METTL3 as a potential therapeutic target for fibrotic disorders.

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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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