Expression of GRIM 19 in adenomyosis and its possible role in pathogenesis

Capsule:
Decreased expression of GRIM-19 may play a role in adenomyosis by regulating apoptosis and angiogenesis.

Authors:
Jing Wang, M.Sc., Xiaohui Deng, Ph.D., Yang Yang, M.Sc., Xingsheng Yang, Ph.D., Beihua Kong, Ph.D., Lan Chao, Ph.D.

Volume 105, Issue 4, Pages 1092-1101

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.

Design:
Experimental study using human samples and cell lines.

Setting:
University-affiliated hospital.

Patient(s):
Ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis, whereas normal endometrial specimens were obtained from 10 control patients without adenomyosis.

Intervention(s):
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.

Main Outcome Measure(s):
Immunohistochemistry (IHC) was performed to evaluate the expression of GRIM-19, phospho-STAT3(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.

Result(s):
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.

Conclusion(s):
Aberrant expression of GRIM-19 may be associated with adenomyosis through the regulation of apoptosis and angiogenesis.

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