title: HMGB1-RAGE signaling pathway in severe preeclampsia.
abstract: BACKGROUND
  Placental dysfunction and increased inflammation are believed to underlie the pathogenesis of severe preeclampsia (PE). High-mobility group box 1 (HMGB1), a recently identified inflammatory cytokine, has been known to contribute to the development of inflammatory responses in PE. This study intends to elucidate the mechanisms of HMGB1-RAGE signaling pathway in the pathogenesis of PE.
  
  
  METHODS
  The mRNA levels of relative gene of HMGB1 pathway, HMGB1, RAGE and NF-κB p65, were analyzed by real-time PCR in placentas collected from 61 normotensive pregnant women and 64 women with severe PE. Additionally, levels of HMGB1 and RAGE protein were detected in frozen placental specimens by western blot, and the locations of them were evaluated in the well-characterized tissue microarray by immunohistochemistry. ELISA was further used to detect HMGB1 level in maternal serum.
  
  
  RESULTS
  Compared with matched control placentas, the mRNA levels of HMGB1, RAGE and NF-κB p65 were increased in severe preeclamptic placentas. In severe preeclamptic placentas, HMGB1 and RAGE immunoreactivity were increased in the cytoplasm of trophoblast cells. Western blot was employed to further confirm that RAGE protein level was elevated significantly in severe PE group. In addition, there was an increased level of HMGB1 in the maternal serum of severe PE group.
  
  
  CONCLUSIONS
  HMGB1 nuclear-cytoplasmic translocation may induce the binding of HMGB1 to its receptors, consequently, intrigue NF-κB activity in severe PE. HMGB1-RAGE signaling pathway may be involved in the pathogenesis of PE.
authors: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan Province, China.
authors: Linlin
authors: L
authors: Zhu
authors: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Shangqiu Medical College, Shangqiu, 476110, Henan Province, China; Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Henan Translational Medicine Engineering Laboratory for Maternal and Children's Health, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China. Electronic address: zhangzhanmd@126.com.
authors: Zhan
authors: Z
authors: Zhang
authors: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Henan Translational Medicine Engineering Laboratory for Maternal and Children's Health, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Linlin
authors: L
authors: Zhang
authors: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Ying
authors: Y
authors: Shi
authors: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Henan Translational Medicine Engineering Laboratory for Maternal and Children's Health, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Jiahui
authors: J
authors: Qi
authors: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Henan Translational Medicine Engineering Laboratory for Maternal and Children's Health, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Aimin
authors: A
authors: Chang
authors: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Junjun
authors: J
authors: Gao
authors: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Yang
authors: Y
authors: Feng
authors: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
authors: Xiaoqian
authors: X
authors: Yang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C000593871:AGER protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D051996:Transcription Factor RelA
keywords: HMGB1; Inflammation; NF-κB; Placenta; RAGE; Severe preeclampsia