These authors contributed equally to this work.
MicroRNA-320 EXPRESSION IN MYOCARDIAL MICROVASCULAR ENDOTHELIAL CELLS AND ITS RELATIONSHIP WITH INSULIN-LIKE GROWTH FACTOR-1 IN TYPE 2 DIABETIC RATS
Article first published online: 28 SEP 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd
Clinical and Experimental Pharmacology and Physiology
Volume 36, Issue 2, pages 181–188, February 2009
How to Cite
Wang, X., Qian, R., Zhang, W., Chen, S., Jin, H. and Hu, R. (2009), MicroRNA-320 EXPRESSION IN MYOCARDIAL MICROVASCULAR ENDOTHELIAL CELLS AND ITS RELATIONSHIP WITH INSULIN-LIKE GROWTH FACTOR-1 IN TYPE 2 DIABETIC RATS. Clinical and Experimental Pharmacology and Physiology, 36: 181–188. doi: 10.1111/j.1440-1681.2008.05057.x
- Issue published online: 27 JAN 2009
- Article first published online: 28 SEP 2008
- Received 16 March 2008; revision 17 July 2008; accepted 25 July 2008.
- insulin-like growth factor 1;
- myocardial microvascular endothelial cells;
- type 2 diabetes
- 1The aim of the present study was to determine the role of myocardial microvascular endothelial cells (MMVEC) in impaired angiogenesis of type 2 diabetic Goto-Kakizaki (GK) rats.
- 2A microRNA (miRNA) microarray was used to assess miRNA expression in MMVEC from GK and Wistar rats. Upregulation of miRNA-320 was observed in MMVEC from GK rats using real-time reverse transcription–polymerase chain reaction (RT-PCR).
- 3So far, nine miRNAs have been reported to target angiogenic factors and/or receptors, including kinase insert domain containing receptor (Flk-1), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 1 receptor (IGF-1R). The predicted genes targeted by miR-320 include Flk-1, IGF-1 and IGF-1R. Western blot analysis and RT-PCR were used to analyse the protein and mRNA expression, respectively, of the putative genes IGF-1 and IGF-1R. The expression of IGF-1 and IGF-1R proteins decreased significantly in diabetic MMVEC. However, the expression of IGF-1 mRNA increased rather than decreased. The mRNA expression of IGF-1R did not differ significantly between diabetic and control MMVEC.
- 4Transfection of an miR-320 inhibitor into MMVEC from GK rats confirmed that miR-320 impaired angiogenesis. The proliferation and migration of diabetic MMVEC improved after transfection of the miR-320 inhibitor. In addition, the miR-320 inhibitor significantly increased the expression of IGF-1 protein, but had no effect on the expression of IGF-1R.
- 5Eleven miRNAs were upregulated in MMVEC from GK rats compared with those in Wistar rats: let-7e, miR-129, miR-291-5p, miR-320, miR-327, mir-333, miR-363–5p, miR-370, miR-494, miR-503 and miR-664.
- 6The results indicate that upregulation of miR-320 in MMVEC from GK rats may be responsible for the inconsistency between the expression of IGF-1 protein and mRNA and therefore related to impaired angiogenesis in diabetes. Transfection of an miR-320 inhibitor may be a therapeutic approach for the treatment of impaired angiogenesis in diabetes.