KIAA1429 Promotes Keloid Formation Through the TGF-Β1/Smad Pathway.

IF 2.2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Current molecular medicine Pub Date : 2024-11-07 DOI:10.2174/0115665240307157241104095116

Shuai Ren, Yingchang Ji, Mengmeng Wang, Maodong Ye, Lvdong Huang, Xiangna Cai

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Abstract

Background: Keloid formation is characterized by excessive production of extracellular matrix, leading to dysregulated fibroproliferative collagen response. N6- methyl-adenosine (m6A) modification plays an essential role in this process.

Objective: Our objective in this study was to explore the mechanism of m6A methyltransferase KIAA1429 in keloid formation.

Methods: We examined the impact of m6A methyltransferase KIAA1429 on keloid formation using qRT-PCR, Western blot, immunofluorescence, Transwell migration assay, and MeRIP-qPCR.

Results: KIAA1429 was downregulated in keloid tissue. Overexpression of KIAA1429 suppressed fibroblast migration and reduced COL1A1 and α-SMA levels. Conversely, the knockdown of KIAA1429 promoted fibroblast migration and COL1A1 and α-SMA levels. Additionally, overexpression of KIAA1429 inhibited the TGF-β1/Smad pathway. Mechanistic experiments suggested that KIAA1429 regulated TGF-β1 m6A modification, maintained TGF-β1 mRNA stability, and participated in the regulation of keloid formation. Furthermore, TGF-β1 could reverse the effects of KIAA1429 overexpression on fibroblast migration and collagen deposition.

Conclusion: Taken together, our study suggested that KIAA1429 promoted keloid formation through the TGF-β1/Smad pathway, providing new insights for the treatment of keloid.

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KIAA1429 通过 TGF-Β1/Smad 途径促进瘢痕疙瘩的形成

背景：瘢痕疙瘩形成的特点是细胞外基质过度生成，导致纤维增生性胶原反应失调。N6-甲基腺苷（m6A）修饰在这一过程中起着至关重要的作用：本研究旨在探讨 m6A 甲基转移酶 KIAA1429 在瘢痕疙瘩形成过程中的作用机制：方法：我们使用qRT-PCR、Western印迹、免疫荧光、Transwell迁移试验和MeRIP-qPCR检测了m6A甲基转移酶KIAA1429对瘢痕疙瘩形成的影响：结果：KIAA1429在瘢痕疙瘩组织中下调。过表达 KIAA1429 可抑制成纤维细胞的迁移，降低 COL1A1 和 α-SMA 的水平。相反，KIAA1429的敲除促进了成纤维细胞的迁移以及COL1A1和α-SMA的水平。此外，KIAA1429的过表达抑制了TGF-β1/Smad通路。机理实验表明，KIAA1429调节了TGF-β1 m6A的修饰，维持了TGF-β1 mRNA的稳定性，并参与了瘢痕疙瘩形成的调节。此外，TGF-β1能逆转KIAA1429过表达对成纤维细胞迁移和胶原沉积的影响：综上所述，我们的研究表明，KIAA1429通过TGF-β1/Smad途径促进瘢痕疙瘩的形成，为瘢痕疙瘩的治疗提供了新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular medicine 医学-医学：研究与实验

CiteScore

5.00

自引率

4.00%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.