{"title":"METTL3通过m6A RNA甲基化GRAMD1B mRNA促进增生性瘢痕纤维化。","authors":"Wanli Guo, Wei Song, Yanbin Zhai, Peiyi Bai, Zhihui Guo, Xiaorui Tian, Peng Duan","doi":"10.1007/s10735-025-10475-7","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"195"},"PeriodicalIF":2.2000,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"METTL3 promotes the hypertrophic scar fibrosis via m6A RNA methylation of GRAMD1B mRNA.\",\"authors\":\"Wanli Guo, Wei Song, Yanbin Zhai, Peiyi Bai, Zhihui Guo, Xiaorui Tian, Peng Duan\",\"doi\":\"10.1007/s10735-025-10475-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":650,\"journal\":{\"name\":\"Journal of Molecular Histology\",\"volume\":\"56 3\",\"pages\":\"195\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Histology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s10735-025-10475-7\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10735-025-10475-7","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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.
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.