EGFR/ERK/MMP-2通路调控牙龈纤维化的初步研究
Preliminary study on regulation of gingival fibrosis by EGFR/ERK/MMP-2 pathway
张晓红 1李生婷 2常群安3
作者信息
- 1. 810006 西宁 青海省妇女儿童医院口腔科
- 2. 青海省第五人民医院口腔科
- 3. 青海大学附属医院口腔颌面外科
- 折叠
摘要
目的 探讨表皮生长因子受体/细胞外信号调节激酶/基质金属蛋白酶-2(EGFR/ERK/MMP-2)通路调控牙龈纤维化的作用机制.方法 收集本院 4 例因畸形治疗的健康者和 4 例遗传性牙龈纤维瘤病(HGF)患者牙龈组织标本;苏木素-伊红(HE)染色检测牙龈组织的组织学变化情况;蛋白质免疫印迹检测牙龈组织中EGFR蛋白表达情况.体外培养人牙龈成纤维细胞(HGFs),并分为对照组、EGFR激动剂组、EGFR抑制剂组,EGFR激动剂组添加终浓度为 10 ng/ml EGF,EGFR抑制剂组添加终浓度为 10 μmol/L AG1478,对照组添加10%胎牛血清的DMEM培养液培养细胞,处理48 h后,蛋白质免疫印迹检测细胞中EGFR、ERK1/2、p-ERK1/2、MMP-2 蛋白水平;CCK-8 法检测细胞增殖情况.结果 HGF患者牙龈组织充满粗大的胶原纤维和成纤维细胞,血管偏少,结缔组织处出现轻微炎症.与健康者相比,HGF患者牙龈组织中EGFR蛋白水平升高(P＜0.05).在细胞实验中,与对照组相比,EGFR激动剂组细胞中EGFR、p-ERK1/2/ERK1/2、MMP-2 蛋白水平及细胞增殖率升高(P<0.05),EGFR抑制剂组细胞中EGFR、p-ERK1/2/ERK1/2、MMP-2 蛋白水平及细胞增殖率降低(P<0.05).结论 EGFR/ERK/MMP-2 通路可能通过促进细胞增殖加强牙龈纤维化进程,抑制EGFR的表达从而缓解疾病.
Abstract
Objective To investigate the mechanism of epidermal growth factor receptor/extracellular signal-regulated kinase/matrix metalloproteinase-2(EGFR/ERK/MMP-2)pathway regulating gingival fibrosis.Methods The gingival tissue samples from 4 healthy people and 4 patients with hereditary gingival fibromatosis(HGF)were collected.Hematoxylin-eosin(HE)staining was used to detect the histological changes of the gingival tissues.Western blot was used to detect EGFR protein expression in gingival tissue.Human gingival fibroblasts(HGFs)were cultured in vitro and divided into control group,EGFR agonist group,and EGFR inhibitor group.The EGFR agonist group was supplemented with a final concentration of 10 ng/ml EGF and EGFR inhibitor group was supplemented with a final concentration of 10 μmol/L,the cells in the control group were cultured in DMEM medium with 10%fetal bovine serum.After 48 h treatment,the protein levels of EGFR,ERK1/2,p-ERK1/2 and MMP-2 were examined by Western blot.CCK-8 method was use to detect cell proliferation.Results The gingival tissue of HGF patients was full of thick collagen fibers and fibroblasts,and there were few blood vessels,and there was slight inflammation in the connective tissue.Compared with healthy people,the EGFR protein level in the gingival tissue of HGF patients increased(P<0.05).Compared with the control group,the EGFR,p-ERK1/2/ERK1/2,MMP-2 protein levels and cell proliferation rate in the EGFR agonist group increased(P<0.05),and EGFR,p-ERK1/2/ERK1/2,MMP-2 protein levels and cell proliferation rate in the EGFR inhibitor group decreased(P<0.05).Conclusions The EGFR/ERK/MMP-2 pathway may enhance the gingival fibrosis process by promoting cell proliferation,while inhibiting the expression of EGFR.
关键词
EGFR/ERK/MMP-2通路/牙龈纤维化/遗传性牙龈纤维瘤病Key words
GFR/ERK/MMP-2 pathway/Gingival fibrosis/Hereditary gingival fibromatosis引用本文复制引用
基金项目
青海省科技计划项目(2020-SF-131)
出版年
2024
NETL
NSTL
万方数据