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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C delta in a mouse model of diabetic retinopathy

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Title
Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C delta in a mouse model of diabetic retinopathy
Author
Park, JeongsookKim, HwajinPark, So YunLim, Sun WooKim, Yoon SookLee, Dong HoonRoh, Gu SeobKim, Hyun JoonKang, Sang SooCho, Gyeong JaeJeong, Bo-YoungKwon, H. MooChoi, Wan Sung
Keywords
Aldose reductase; Diabetic retinopathy; Hyperglycemia; Protein kinase C; TonEBP
Issue Date
201405
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation
EXPERIMENTAL EYE RESEARCH, v.122, no., pp.13 - 19
Abstract
Recent studies revealed that Tonicity-responsive enhancer binding protein (TonEBP) directly regulates the transcription of aldose reductase (AR), which catalyzes the first step of the polyol pathway of glucose metabolism. Activation of protein kinase C δ (PKCδ) is dependent on AR and it has been linked to diabetic complications. However, whether TonEBP affects expressions of AR and PKCδ in diabetic retinopathy was not clearly shown. In this study, we used TonEBP heterozygote mice to study the role of TonEBP in streptozotocin (STZ)-induced diabetic retinopathy. We performed immunofluorescence staining and found that retinal expressions of AR and PKCδ were significantly reduced in the heterozygotes compared to wild type littermates, particularly in ganglion cell layer. To examine further the effect of TonEBP reduction in retinal tissues, we performed intravitreal injection of TonEBP siRNA and confirmed the decrease in AR and PKCδ levels. In addition, we found that a proapoptotic factor, Bax level was reduced and a survival factor, Bcl2 level was increased after injection of TonEBP siRNA, indicating that TonEBP mediates apoptotic cell death. In parallel, TonEBP siRNA was applied to the invitro human retinal pigment epithelial (ARPE-19) cells cultured in high glucose media. We have consistently found the decrease in AR and PKCδ levels and changes in apoptotic factors for survival. Together, these results clearly demonstrated that hyperglycemia-induced TonEBP plays a crucial role in increasing AR and PKCδ levels and leading to apoptotic death. Our findings suggest that TonEBP reduction is an effective therapeutic strategy for diabetic retinopathy.
URI
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DOI
http://dx.doi.org/10.1016/j.exer.2014.03.001
ISSN
0014-4835
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