Abstract
BackgroundMatrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion.MethodsWestern blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2.ResultsCAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2.ConclusionsCAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2.
Highlights
Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis
We found that calcium-activated neutral protease 7 (CAPN 7) mRNA and protein expression was upregulated in the eutopic endometrium and endometrial stromal cells from women who were diagnosed with endometriosis, and we further investigated the effects of CAPN 7 on human endometrial stromal cell (hESC) motility and invasion
CAPN 7 expression is increased in endometriosis To determine the role of CAPN 7 in endometriosis, we first examined CAPN 7 expression in endometriosis patients using western blotting and quantitative real-time PCR
Summary
Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. We found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Endometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity [1]. This disease affects approximately 10% of women of reproductive age and is associated with pelvic pain, dysmenorrhea and infertility [1,2]; the exact pathogenesis remains unclear. CAPN 7, a non-classical calpain, lacks the EF-hand domain, and its activity does not depend on Ca2+ [9]; the exact structure and pathological significance of CAPN 7 have not been fully elucidated
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