title: CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  Western 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.
  
  
  RESULTS
  CAPN 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.
  
  
  CONCLUSIONS
  CAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2.
authors.affiliation: Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jin
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Shen
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Junxia
authors.initials: J
authors.lastname: Wang
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D002154:Calpain; C117906:Capn7 protein, human; D020778:Matrix Metalloproteinase 2