Authors: Xie S; Xie N; Li Y; Wang P; Zhang C; Li Q; Liu X; Deng J; Zhang C; Lv C
Abstract: To characterize the roles of tribble 2 (TRB2) and its targeted microRNAs (miRNAs) in the pathogenesis of the early vascular injury involved in diabetic-2 rat. Goto-Kakizaki (GK) rat and Wistar rat were used as the animal models. Each eligible rat was killed and the rat aorta tissues were analyzed by immunohistochemistry, ELISA, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR detection. GFP expression in RAOEC cells (rat vascular aortic endothelial cell)were detected by flow cytometry and fluorescent microscope. TRB2 gene expression was increased in endothelia cell and the adventitia of Goto-Kakizaki (GK) rat compared with Wistar rat. Next, studies using RAOEC cells showed that the TRB2 expression was inhibited by the treatment of miR-98. We further showed that the expression of miR-98 was significantly decreased in the adventitia and endomembrane at different degrees in GK rats compared with control. Finally, we validated the changes in TRB2 by studying one of the TRB2's substrates, Akt, in animal models. We expected a corresponding change in the levels of phosphorylated Akt. Indeed, our results showed that the phosphorylation of Akt at Thr 308 in the endothelial cells and phosphorylation of Akt at Ser 473 in adventitia was decreased in GK rats, compared with Wistar control. TRB2 plays important roles in the pathogenesis of diabetic-2 large artery complications at early stage, and these effects may be modulated by miR-98. Thus, targeting TRB2 and miR-98 could be considered as novel therapeutic strategies for the early large artery deficits in diabetic-2.
Keywords: 3' Untranslated Regions; Animals; Aorta/metabolism/pathology; Aortic Diseases/*etiology/genetics/metabolism; Atherosclerosis/*etiology/genetics/metabolism; Cells, Cultured; Diabetes Mellitus, Type 2/*complications/genetics/metabolism; Diabetic Angiopathies/*etiology/genetics/metabolism; Endothelial Cells/metabolism; Gene Expression; Gene Expression Regulation; Genes, Reporter; Green Fluorescent Proteins/biosynthesis/genetics; Intracellular Signaling Peptides and Proteins/*genetics/metabolism; Male; MicroRNAs/*genetics/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Rats; Rats, Wistar; *Up-Regulation|
Journal: Molecular and cellular biochemistry Volume: 361 Issue: 1-2 Pages: 305-14 Date: Oct. 21, 2011 PMID: 22012613 |
Xie S, Xie N, Li Y, Wang P, Zhang C, Li Q, Liu X, Deng J, Zhang C, Lv C (2012) Upregulation of TRB2 induced by miR-98 in the early lesions of large artery of type-2 diabetic rat. Molecular and cellular biochemistry 361: 305-14.
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