The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy
Tóm tắt
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. 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. 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. 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.
Tài liệu tham khảo
Antonetti DA, Klein R, Gardner TW: Diabetic retinopathy. N Engl J Med 2012, 366: 1227-1239. 10.1056/NEJMra1005073
International Diabetes Federation: IDF Diabetes Atlas. 6th edition. Brussels, Belgium: International Diabetes Federation; 2013.http://www.idf.org/diabetesatlas
Cheung N, Mitchell P, Wong TY: Diabetic retinopathy. Lancet 2010, 376: 124-136. 10.1016/S0140-6736(09)62124-3
Dvoriantchikova G, Hernandez E, Grant J, Santos AR, Yang H, Ivanov D: The high-mobility group box-1 nuclear factor mediates retinal injury after ischemia reperfusion. Invest Ophthalmol Vis Sci 2011, 52: 7187-7194. 10.1167/iovs.11-7793
van Beijnum JR, Buurman WA, Griffioen AW: Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis 2008, 11: 91-99. 10.1007/s10456-008-9093-5
Anfuso CD, Assero G, Lupo G, Nicotra A, Cannavo’ G, Strosznajder RP, Rapisarda P, Pluta R, Alberghina M: Amyloid beta(1–42) and its beta(25–35) fragment induce activation and membrane translocation of cytosolic phospholipase A2 in bovine retina capillary pericytes. Biochim Biophys Acta 2004, 1686: 125-138. 10.1016/j.bbalip.2004.09.006
Nicotra A, Lupo G, Giurdanella G, Anfuso CD, Ragusa N, Tirolo C, Marchetti B, Alberghina M: MAPKs mediate the activation of cytosolic phospholipase A2 by amyloid beta(25–35) peptide in bovine retina pericytes. Biochim Biophys Acta 2005, 1733: 172-186. 10.1016/j.bbalip.2004.12.017
Singh NK, Hansen DE 3rd, Kundumani-Sridharan V, Rao GN: Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCg-cPLA(2) activation and retinal neovascularization. Blood 2013, 121: 1911-1923. 10.1182/blood-2012-03-419234
Kajdaniuk D, Marek B, Foltyn W, Kos-Kudła B: Vascular endothelial growth factor (VEGF) – Part 1: In physiology and pathophysiology. Endokrynol Pol 2011, 62: 444-455.
Hammes HP, Lin J, Renner O, Shani M, Lundqvist A, Betsholtz C, Brownlee M, Deutsch U: Pericytes and the pathogenesis of diabetic retinopathy. Diabetes 2002, 51: 3107-3112. 10.2337/diabetes.51.10.3107
Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP: A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 2004, 18: 1450-1452.
Joussen AM, Doehmen S, Le ML, Koizumi K, Radetzky S, Krohne TU, Poulaki V, Semkova I, Kociok N: TNF alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Mol Vis 2009, 15: 1418-1428.
Giurdanella G, Motta C, Muriana S, Arena V, Anfuso CD, Lupo G, Alberghina M: Cytosolic and calcium-independent phospholipase A2 mediate glioma enhanced proangiogenic activity of brain endothelial cells. Microvasc Res 2011, 81: 1-17. 10.1016/j.mvr.2010.11.005
Lupo G, Anfuso CD, Ragusa N, Strosznajder RP, Walski M, Alberghina M: t-Butyl hydroperoxide and oxidized low density lipoprotein enhance phospholipid hydrolysis in lipopolysaccharide-stimulated retinal pericytes. Biochim Biophys Acta 2001, 1531: 143-155. 10.1016/S1388-1981(01)00102-0
Gavrieli Y, Gavrieli Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992, 119: 493-501. 10.1083/jcb.119.3.493
Bucolo C, Leggio GM, Drago F, Salomone S: Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Biochem Pharmacol 2012, 84: 88-92. 10.1016/j.bcp.2012.03.019
Elanchezhian R, Palsamy P, Madson CJ, Lynch DW, Shinohara T: Age-related cataracts: homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection. Chem Biol Interact 2012, 200: 1-10. 10.1016/j.cbi.2012.08.017
Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL 3rd, Klein R: Retinopathy in diabetes. Diabetes Care 2004, 27(1):S84-S87.
Ferrara N: Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004, 25: 581-611. 10.1210/er.2003-0027
El-Asrar AM, Missotten L, Geboes K: Expression of high-mobility groups box-1/receptor for advanced glycation end products/osteopontin/early growth response-1 pathway in proliferative vitreoretinal epiretinal membranes. Mol Vis 2011, 17: 508-518.
Abu El-Asrar AM, Nawaz MI, Kangave D, Abouammoh M, Mohammad G: High-mobility group box-1 and endothelial cell angiogenic markers in the vitreous from patients with proliferative diabetic retinopathy. MediatoInflamm 2012, 2012: 697489.
Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ: HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 2010, 28: 367-388. 10.1146/annurev.immunol.021908.132603
Lin Q, Yang XP, Fang D, Ren X, Zhou H, Fang J, Liu X, Zhou S, Wen F, Yao X, Wang JM, Su SB: High-mobility group box-1 mediates toll-like receptor 4-dependent angiogenesis. Arterioscler Thromb Vasc Biol 2011, 31: 1024-1032. 10.1161/ATVBAHA.111.224048
Wang J, Kolko M: Phospholipases A2 in ocular homeostasis and diseases. Biochimie 2010, 92: 611-619. 10.1016/j.biochi.2010.04.007
Kolko M, Wang J, Zhan C, Poulsen KA, Prause JU, Nissen MH, Heegaard S, Bazan NG: Identification of intracellular phospholipases A2 in the human eye: involvement in phagocytosis of photoreceptor outer segments. Invest Ophthalmol Vis Sci 2007, 48: 1401-1409. 10.1167/iovs.06-0865
Pannicke T, Iandiev I, Wurm A, Uckermann O, vom Hagen F, Reichenbach A, Wiedemann P, Hammes HP, Bringmann A: Diabetes alters osmotic swelling characteristics and membrane conductance of glial cells in rat retina. Diabetes 2006, 55: 633-639. 10.2337/diabetes.55.03.06.db05-1349
Barnett JM, McCollum GW, Penn JS: Role of cytosolic phospholipase A(2) in retinal neovascularization. Invest Ophthalmol Vis Sci 2009, 51: 1136-1142.
Salomone S, Waeber C: Selectivity and specificity of sphingosine-1-phosphate receptor ligands: caveats and critical thinking in characterizing receptormediated effects. Front Pharmacol 2011, 2: 9.
Noda K, Nakao S, Ishida S, Ishibashi T: Leukocyte adhesion molecules in diabetic retinopathy. J Ophthalmol 2012, 2012: 279037.
Witmer AN, Blaauwgeers HG, Weich HA, Alitalo K, Vrensen GF, Schlingemann RO: Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey. Invest Ophthalmol Vis Sci 2002, 43: 849-857.
Greenberg JI, Shields DJ, Barillas SG, Acevedo LM, Murphy E, Huang J, Scheppke L, Stockmann C, Johnson RS, Angle N, Cheresh DA: A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 2008, 456: 809-813. 10.1038/nature07424
Bergers G, Song S: The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 2005, 7: 452-464. 10.1215/S1152851705000232