RESUMO
Endometriosis is a benign disease, with malignant properties. A necessary step in the progression of endometriosis is tissue remodeling, which is coordinated by the activities of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). This study evaluated the regulation of abnormal MMP and TIMP gene expression during endometriosis. Among the two genes families, promoter regions of MMP2, MMP3, MMP7, TIMP3, and TIMP4 were significantly altered in proliferative-phase endometriotic lesions compared to menstrual cycle-matched eutopic tissue from endometriosis-free women. In addition, a negative correlation was found between the DNA methylation status of the promoter region and transcript abundance of MMP2. Our findings suggest that changes in DNA methylation at the promoter region of MMP2 could underlie the changes in its expression in the ectopic endometria from patients with endometriosis.
Assuntos
Metilação de DNA/genética , Endometriose/genética , Metaloproteinase 2 da Matriz/genética , Regiões Promotoras Genéticas/genética , Endometriose/patologia , Feminino , Regulação da Expressão Gênica/genética , Humanos , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 7 da Matriz/genética , Ciclo Menstrual/fisiologia , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidores Teciduais de Metaloproteinases/genética , Inibidor Tecidual 4 de MetaloproteinaseRESUMO
One important function of melanocytes (MCs) is to produce and transfer melanin to neighbouring keratinocytes (KCs) to protect epithelial cells from UV radiation. The mechanisms regulating the specific migration and localisation of the MC lineage remain unknown. We have found three heterozygous mutations that cause amino acid substitutions in the SASH1 gene in individuals with a kind of dyschromatosis. In epidermal tissues from an affected individual, we observed the increased transepithelial migration of melanocytes. Functional analyses indicate that these SASH1 mutations not only cause the increased migration of A375 cells and but also induce intensive bindings with two novel cell adhesion partners IQGAP1 and Gαs. Further, SASH1 mutations induce uniform loss of E-Cadherin in human A375 cells. Our findings suggest a new scaffold protein SASH1 to regulate IQGAP1-E-Cadherin signalling and demonstrate a novel crosstalking between GPCR signalling, calmodulin signalling for the modulation of MCs invasion.
