title: The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy.
abstract: BACKGROUND
  Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy.
  
  
  METHODS
  We performed our study in streptozotocin (STZ)-induced diabetic rat model. The expression levels of the cytokines, chemokines, and cell adhesion molecules in retinal tissues were evaluated by quantitative RT-PCR. HMGB-1 and PLA2 protein levels along with VEGF, TNF-α, IL-1β and ICAM-1 levels were also measured.
  
  
  RESULTS
  We observed the retinal pericytes, endothelial injury/death and breakdown of blood-retinal barrier (BRB). The protein expression of HMGB-1, PLA2 and IL-1β were significantly increased in micro vessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNF-α. Further investigation revealed that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate endothelial cell death. Similarly, increased expression of PLA2 represents the diabetic mediated alteration of BRB, perhaps up regulating the VEGF.
  
  
  CONCLUSIONS
  Our data suggest that HMGB-1 and PLA2 involved in retinal pericyte and endothelial injury and cell death in diabetic retinopathy. From this study, we suggest that HMGB-1 and PLA2 may be interesting targets in managing diabetic retinopathy.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Quan-Shun
authors.initials: QS
authors.lastname: Wang
authors.forename: Shi-Hui
authors.initials: SH
authors.lastname: Wei
authors.forename: Bao-Ke
authors.initials: BK
authors.lastname: Hou
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital, No, 28 Fuxing Road, Haidian District, Beijing 100853, China. zhangmaonian80@gmail.com.
authors.forename: Mao-Nian
authors.initials: MN
authors.lastname: Zhang
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D003930:Diabetic Retinopathy / Q000201:enzymology*; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020286:Pericytes / Q000201:enzymology; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology; D012171:Retinal Vessels / Q000201:enzymology / Q000473:pathology
chemical_list: D018925:Chemokines; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D054467:Phospholipases A2