title: Expression of GRIM-19 in adenomyosis and its possible role in pathogenesis.
abstract: OBJECTIVE
  To study the expression of the gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19) in the endometrial tissue of patients with adenomyosis and to describe the possible pathogenic mechanisms of this phenomenon.
  
  
  METHODS
  Experimental study using human samples and cell lines.
  
  
  METHODS
  University-affiliated hospital.
  
  
  METHODS
  Ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis, whereas normal endometrial specimens were obtained from 10 control patients without adenomyosis.
  
  
  METHODS
  Patients with rapid pathology report-confirmed adenomyosis were recruited, and eutopic and ectopic endometrial tissue samples were collected from patients who had undergone hysterectomies by either the transabdominal or laparoscopic method at Qilu Hospital. Normal endometrial tissue was collected from a group of control patients without adenomyosis.
  
  
  METHODS
  Immunohistochemistry (IHC) was performed to evaluate the expression of GRIM-19, phospho-signal transducer and activator of transcription 3 (Y705) (Y705) (pSTAT3(Y705)), and vascular endothelial growth factor (VEGF) in endometrial tissue samples. The protein levels of GRIM-19, pSTAT3(Y705), STAT3, and VEGF were detected by Western blot. Apoptosis in endometrial specimens was assayed by TUNEL. Immunohistochemistry with an antibody directed against CD34 was performed to detect new blood vessels in the endometrial tissue. GRIM-19 small interfering RNA and a recombinant plasmid carrying GRIM-19 were constructed to evaluate the effects of GRIM-19 on the downstream factors pSTAT3(Y705), STAT3, and VEGF in Ishikawa cells.
  
  
  RESULTS
  The expression of GRIM-19 was down-regulated in the eutopic endometria of patients with adenomyosis compared with the endometria of patients in the control group, and it was further reduced in the endometrial glandular epithelial cells of adenomyotic lesions. Apoptosis was reduced in the eutopic endometrium compared with the control group, and it was significantly reduced in ectopic endometrial tissues. In addition, the ectopic and eutopic endometria of patients with adenomyosis displayed a much higher microvessel density. In the eutopic and ectopic endometria of patients with adenomyosis, the expression levels of pSTAT3(Y705) and VEGF were significantly higher than in the controls. Furthermore, down-regulation of GRIM-19 in Ishikawa cells significantly promoted the activation of both pSTAT3(Y705) and its dependent gene VEGF.
  
  
  CONCLUSIONS
  Aberrant expression of GRIM-19 may be associated with adenomyosis through the regulation of apoptosis and angiogenesis.
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Deng
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China. Electronic address: qlszcl@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Chao
mesh_terms: D062788:Adenomyosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human
keywords: GRIM-19; adenomyosis; angiogenesis; apoptosis