甲基化CpG结合蛋白2通过调节解聚素和金属蛋白酶12的表达及Wnt/β-连环蛋白信号通路促进瘢痕疙瘩进展。
MeCP2 promotes keloid progression by regulating ADAM12 expression and Wnt/β-catenin pathway.
作者信息
Xiao Yuzhou, Lin Nan, Chen Huaxia, Xiao Hu
机构信息
Department of Burns and Plastic Surgery, Shandong Provincial Hospital, Shandong University, Jinan City, 250021, Shandong, China.
Department of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324, Jingwu Road, Huaiyin District, Jinan City, 250021, Shandong, China.
出版信息
Arch Dermatol Res. 2025 Mar 22;317(1):621. doi: 10.1007/s00403-025-04131-z.
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.
背景
据报道，甲基化CpG结合蛋白2（MeCP2）参与人类疾病的进展。在本研究中，我们旨在探讨MeCP2在瘢痕疙瘩进展中的功能及相关机制。
方法
采用qRT-PCR和蛋白质免疫印迹法检测MeCP2和去整合素金属蛋白酶12（ADAM12）的表达。通过CCK-8法检测细胞增殖情况。采用Transwell法检测细胞迁移和侵袭能力。通过流式细胞术分析细胞凋亡情况。采用染色质免疫沉淀RT-PCR法和双荧光素酶报告基因检测法分析ADAM12与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。ADAM12基因沉默可抑制瘢痕疙瘩成纤维细胞的增殖、迁移、侵袭、细胞外基质积累，促进细胞凋亡，并阻断Wnt/β-连环蛋白信号通路。此外，我们证实MeCP2可通过结合ADAM12启动子来调节其表达。MeCP2基因敲低可抑制瘢痕疙瘩成纤维细胞的增殖、迁移、侵袭和细胞外基质积累，而ADAM12过表达可改善这些作用。此外，MeCP2基因沉默通过改变ADAM12的表达抑制Wnt/β-连环蛋白信号通路。
结论
MeCP2通过调节ADAM12的表达和Wnt/β-连环蛋白信号通路来促进瘢痕疙瘩成纤维细胞的增殖、迁移、侵袭和细胞外基质积累。
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