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IF 1.8 4区医学 Q3 DERMATOLOGY

Archives of Dermatological Research Pub Date : 2025-03-22 DOI:10.1007/s00403-025-04131-z

Yuzhou Xiao, Nan Lin, Huaxia Chen, Hu Xiao

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引用次数: 0

摘要

背景：据报道，甲基 CpG 结合蛋白 2（MeCP2）参与了人类疾病的进展。本研究旨在探讨 MeCP2 在瘢痕疙瘩进展中的功能及相关机制。研究方法通过qRT-PCR和Western印迹检测MeCP2和A分解蛋白和金属蛋白酶12（ADAM12）的表达。细胞增殖采用 CCK-8 检测法。细胞迁移和侵袭通过跨孔试验进行检测。流式细胞术分析了细胞凋亡。通过CHIP RT-PCR检测和双荧光素酶报告分析了ADAM12和MeCP2之间的关系。结果ADAM12在瘢痕疙瘩组织和瘢痕疙瘩成纤维细胞中高表达。沉默 ADAM12 可抑制瘢痕疙瘩成纤维细胞的增殖、迁移、侵袭、ECM 积累，促进细胞凋亡，阻断 Wnt/β-catenin 通路。此外，我们还验证了MeCP2可通过与其启动子结合来调节ADAM12的表达。敲除MeCP2可抑制瘢痕疙瘩成纤维细胞的增殖、迁移、侵袭和ECM积累，而过表达ADAM12则可改善其效果。此外，沉默 MeCP2 还能通过改变 ADAM12 的表达抑制 Wnt/β-catenin 通路。结论MeCP2调控ADAM12的表达和Wnt/β-catenin通路，促进瘢痕疙瘩成纤维细胞的增殖、迁移、侵袭和ECM积累。

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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MeCP2 promotes keloid progression by regulating ADAM12 expression and Wnt/β-catenin pathway

Background: Methyl-CpG binding protein 2 (MeCP2) has been reported to participate in the progression of human diseases. In this study, we aimed to explore the functions and related mechanisms of MeCP2 in keloid progression. Methods: Expression of MeCP2 and A Disintegrin and Metalloprotease 12 (ADAM12) was measured by qRT-PCR and western blot assay. Cell proliferation was explored by CCK-8 assay. Cell migration and invasion were investigated by transwell assay. Cell apoptosis was analyzed by flow cytometry analysis. The relation between ADAM12 and MeCP2 was analyzed by CHIP RT-PCR assay and dual-luciferase reporter assay. Results: ADAM12 was highly expressed in keloid tissues and keloid fibroblasts. Silencing of ADAM12 suppressed the proliferation, migration, invasion, ECM accumulation, facilitated the apoptosis and blocked Wnt/β-catenin pathway in keloid fibroblasts. Furthermore, we verified that MeCP2 could modulate ADAM12 expression by binding to its promoter. MeCP2 knockdown inhibited keloid fibroblasts proliferation, migration, invasion and ECM accumulation, with ADAM12 overexpression ameliorated the effects. Besides, MeCP2 silencing inhibited Wnt/β-catenin pathway by altering ADAM12 expression. Conclusion: MeCP2 regulated ADAM12 expression and Wnt/β-catenin pathway to promote cell proliferation, migration, invasion and ECM accumulation in keloid fibroblasts.

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来源期刊

Archives of Dermatological Research 医学-皮肤病学

CiteScore

4.10

自引率

3.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Archives of Dermatological Research is a highly rated international journal that publishes original contributions in the field of experimental dermatology, including papers on biochemistry, morphology and immunology of the skin. The journal is among the few not related to dermatological associations or belonging to respective societies which guarantees complete independence. This English-language journal also offers a platform for review articles in areas of interest for dermatologists and for publication of innovative clinical trials.