Abstract
Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor (VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid (P <.001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control (P <.05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 1532-1537 |
| Number of pages | 6 |
| Journal | Reproductive Sciences |
| Volume | 24 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2017 |
Fingerprint
Keywords
- endometriosis
- high-mobility group box 1
- lipopolysaccharide
- receptor for advanced glycation end products
- vascular endothelial growth factor
ASJC Scopus subject areas
- Obstetrics and Gynaecology
Cite this
High Expression of High-Mobility Group Box 1 in Menstrual Blood : Implications for Endometriosis. / Shimizu, Keiko; Kamada, Yasuhiko; Sakamoto, Ai; Matsuda, Miwa; Nakatsuka, Mikiya; Hiramatsu, Yuji.
In: Reproductive Sciences, Vol. 24, No. 11, 01.11.2017, p. 1532-1537.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High Expression of High-Mobility Group Box 1 in Menstrual Blood
T2 - Implications for Endometriosis
AU - Shimizu, Keiko
AU - Kamada, Yasuhiko
AU - Sakamoto, Ai
AU - Matsuda, Miwa
AU - Nakatsuka, Mikiya
AU - Hiramatsu, Yuji
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor (VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid (P <.001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control (P <.05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.
AB - Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor (VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid (P <.001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control (P <.05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.
KW - endometriosis
KW - high-mobility group box 1
KW - lipopolysaccharide
KW - receptor for advanced glycation end products
KW - vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=85031302628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031302628&partnerID=8YFLogxK
U2 - 10.1177/1933719117692042
DO - 10.1177/1933719117692042
M3 - Article
C2 - 29017437
AN - SCOPUS:85031302628
VL - 24
SP - 1532
EP - 1537
JO - Reproductive Sciences
JF - Reproductive Sciences
SN - 1933-7191
IS - 11
ER -