CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity

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.

Krüppel-like factor 12 is a novel negative regulator of forkhead box O1 expression: a potential role in impaired decidualization

“…Human endometrial stromal cells (hESCs) were isolated and cultured as described previously, and the purity of the cultured stromal cells was determined by cell immunohistochemistry, as shown in Additional file 1 : Figure S1. Decidualization was induced according to a previously published protocol [ 19 , 20 ].…”

MicroRNA-181a is involved in the regulation of human endometrial stromal cell decidualization by inhibiting Krüppel-like factor 12

“…hESC were isolated from the mid-secretory phase of endometrial tissue of women with a normal menstrual cycle by endometrial biopsy. hESC were isolated and cultured as previously described [ 23 ].…”

“…Briefly, protein extracts were prepared from hESC as previously described [ 23 ]. Equal amounts of total protein (30 μg) were separated on a 10% SDS-polyacrylamide gel and transferred onto polyvinylidene fluoride membranes (Millipore, Billerica, MA, USA).…”

Age at Menarche and Oxidative Stress Markers in Women with Endometriosis

“…MMP-2 and MMP-9 have the ability of degradation of type IV collagen. Additionally, many studies have proved that MMP-2 and MMP-9 play an important role in angiogenesis, metastasis, and invasion in many diseases such as cancer and endometriosis [13,14].…”