title: High glucose-induced downregulation of connexin 30.2 promotes retinal vascular lesions: implications for diabetic retinopathy.
abstract: OBJECTIVE
  To investigate whether high glucose (HG) alters expression of connexin 30.2 (Cx30.2) and influences gap junction intercellular communication (GJIC) in retinal endothelial cells and promotes vascular lesions characteristic of diabetic retinopathy (DR).
  
  
  METHODS
  Western blot analysis and immunostaining were performed to determine Cx30.2 protein expression and localization in rat retinal endothelial cells (RRECs) grown in normal (N; 5 mM) or HG (30 mM) medium for 7 days. Concurrently, GJIC was assessed in cells grown in N or HG medium and in cells transfected with Cx30.2 siRNA. Similarly, retinal Cx30.2 expression was assessed in nondiabetic and diabetic rats. Additionally, the effect of reduced Cx30.2 on development of acellular capillaries (ACs) and pericyte loss (PL) was studied in retinas of Cx30.2 knockout mice.
  
  
  RESULTS
  Cx30.2 was identified in RRECs in vitro and in vascular cells of retinal capillaries. RRECs grown in HG exhibited significantly reduced Cx30.2 protein levels consistent with decreased Cx30.2 immunostaining compared with those grown in N medium. Cells grown in HG and cells transfected with Cx30.2 siRNA exhibited significantly diminished dye transfer compared with N or nontransfected cells. Importantly, Cx30.2 protein level and immunostaining were decreased in diabetic retinas compared with nondiabetic retinas. Retinal capillaries of Cx30.2 knockout mice exhibited increased numbers of ACs and PL compared with those of wild-type mice.
  
  
  CONCLUSIONS
  These results indicate that HG- or diabetes-induced downregulation of Cx30.2 expression and decrease in GJIC activity play a critical role in the development of retinal vascular lesions in early DR.
authors: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: Julia
authors: J
authors: Manasson
authors: Thomas
authors: T
authors: Tien
authors: Colleen
authors: C
authors: Moore
authors: Nalin M
authors: NM
authors: Kumar
authors: Sayon
authors: S
authors: Roy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D000075302:Connexin 30; D017630:Connexins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000075302:Connexin 30; D017630:Connexins; C508770:Gjb6 protein, rat; C510757:connexin 30.2, mouse; D005947:Glucose
references: Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3758-63
references: 20130277
references: J Comp Neurol. 1998 Jul 6;396(3):310-21
references: 9624586
references: Mol Vis. 2011;17:3166-74
references: 22171163
references: J Dent Res. 2010 Feb;89(2):116-27
references: 20042738
references: Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1400-7
references: 19029021
references: BJU Int. 2009 Jun;103(12):1686-93
references: 19154470
references: Brain Res Brain Res Rev. 2000 Apr;32(1):138-45
references: 10751663
references: N Engl J Med. 2004 Jan 1;350(1):48-58
references: 14702427
references: Cardiovasc Res. 2004 May 1;62(2):228-32
references: 15094343
references: Biochim Biophys Acta. 2012 Aug;1818(8):1971-84
references: 22044799
references: Biochem Biophys Res Commun. 2008 May 2;369(2):388-94
references: 18291099
references: Clin Exp Pharmacol Physiol. 2002 Jul;29(7):620-5
references: 12060107
references: Invest Ophthalmol Vis Sci. 2011 Feb 28;52(2):1156-63
references: 21357409
references: Curr Eye Res. 2011 Aug;36(8):747-53
references: 21780924
references: Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5376-82
references: 14638741
references: Pharmacol Ther. 2004 Aug;103(2):167-77
references: 15369682
references: Vis Neurosci. 2010 Jul;27(3-4):91-101
references: 20537217
references: Diabetes. 2006 Jan;55(1):86-92
references: 16380480
references: Exp Cell Res. 1987 Feb;168(2):422-30
references: 2433137
references: Biochem Biophys Res Commun. 2007 Oct 26;362(3):747-52
references: 17761141
references: Int J Cancer. 2000 Jan 15;85(2):281-8
references: 10629090
references: Antioxid Redox Signal. 2009 Feb;11(2):251-66
references: 18831678
references: FEBS Lett. 2003 Apr 10;540(1-3):151-6
references: 12681499
references: Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1915-20
references: 11431461
references: J Neurosci Res. 2011 Dec;89(12):2052-67
references: 21567444
references: Curr Diab Rep. 2011 Aug;11(4):253-64
references: 21611764
references: Diabetes. 2002 May;51(5):1565-71
references: 11978657
references: Lancet. 2010 Jul 10;376(9735):124-36
references: 20580421
references: Cell. 1996 Feb 9;84(3):381-8
references: 8608591
references: J Biol Chem. 2004 Jun 25;279(26):27219-24
references: 15123628