High Glucose Alters Retinal Astrocytes Phenotype through Increased Production of Inflammatory Cytokines and Oxidative Stress

作者: Eui Seok Shin , Qiong Huang , Zafer Gurel , Christine M. Sorenson , Nader Sheibani

DOI: 10.1371/JOURNAL.PONE.0103148

关键词: RetinalCell biologyCell adhesionOxidative stressRetinaMatrigelInflammationProinflammatory cytokineSignal transductionBiologyGeneral Biochemistry, Genetics and Molecular BiologyGeneral Agricultural and Biological SciencesGeneral Medicine

摘要: Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance blood-retina-barrier (BRB). Diabetes affects physiology function vascular including astrocytes (AC) leading to breakdown BRB. However, detailed cellular mechanisms AC dysfunction under high glucose conditions remain unclear. Here we show did not induce apoptosis AC, but instead increased their rate DNA synthesis adhesion extracellular matrix proteins. These alterations were associated with changes intracellular signaling pathways involved cell survival, migration proliferation. High also affected expression inflammatory cytokines activated NF-κB, prevented network formation on Matrigel. In addition, showed attenuation conditions, capillary morphogenesis endothelial Matrigel, was mediated through oxidative stress. Antioxidant proteins heme oxygenase-1 peroxiredoxin-2 levels nuclear localization transcription factor factor-erythroid 2-related factor-2. Together our results demonstrated alter by production stress significant impact proliferation, adhesion, migration.

参考文章(47)
W. A. Frazier, Nader Sheibani, Thrombospondin-1, PECAM-1, and regulation of angiogenesis. Histology and Histopathology. ,vol. 14, pp. 285- 294 ,(1999) , 10.14670/HH-14.285
Christine M Sorenson, Shoujian Wang, Robert Gendron, Hélène Paradis, Nader Sheibani, Thrombospondin-1 Deficiency Exacerbates the Pathogenesis of Diabetic Retinopathy. Journal of diabetes & metabolism. ,vol. 2013, pp. 1- 9 ,(2013) , 10.4172/2155-6156.S12-005
J P Ways, M M Godlevski, J G Gray, J P Cogswell, W C Clay, G B Wisely, L M Leesnitzer, NF-kappa B regulates IL-1 beta transcription through a consensus NF-kappa B binding site and a nonconsensus CRE-like site. Journal of Immunology. ,vol. 153, pp. 712- 723 ,(1994)
David R. Clemmons, Laura A. Maile, Yan Ling, J. Yarber, Walker H. Busby, Role of the integrin αVβ3 in mediating increased smooth muscle cell responsiveness to IGF-I in response to hyperglycemic stress Growth Hormone & Igf Research. ,vol. 17, pp. 265- 270 ,(2007) , 10.1016/J.GHIR.2007.01.004
Jiawen Fan, Gezhi Xu, Tingting Jiang, Yaowu Qin, Pharmacologic induction of heme oxygenase-1 plays a protective role in diabetic retinopathy in rats. Investigative Ophthalmology & Visual Science. ,vol. 53, pp. 6541- 6556 ,(2012) , 10.1167/IOVS.11-9241
G SERINI, D VALDEMBRI, F BUSSOLINO, Integrins and angiogenesis: a sticky business. Experimental Cell Research. ,vol. 312, pp. 651- 658 ,(2006) , 10.1016/J.YEXCR.2005.10.020
Tammy L. Palenski, Christine M. Sorenson, Nader Sheibani, Inflammatory cytokine-specific alterations in retinal endothelial cell function. Microvascular Research. ,vol. 89, pp. 57- 69 ,(2013) , 10.1016/J.MVR.2013.06.007
A. Elobeid, E. Bongcam-Rudloff, B. Westermark, M. Nist�r, Effects of inducible glial fibrillary acidic protein on glioma cell motility and proliferation. Journal of Neuroscience Research. ,vol. 60, pp. 245- 256 ,(2000) , 10.1002/(SICI)1097-4547(20000415)60:2<245::AID-JNR14>3.0.CO;2-1
J. Middeldorp, E.M. Hol, GFAP in Health and Disease Progress in Neurobiology. ,vol. 93, pp. 421- 443 ,(2011) , 10.1016/J.PNEUROBIO.2011.01.005