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 - Tập 36 Số 2 - Trang 181-188 - 2009
Wang Xh1,2, R Qian1,2, W Zhang1, SF Chen1,3, Jin Hm1, R.M. Hu4,3
1Department of Physiology and Pathophysiology, Shanghai Medical College and
2these authors contributed equally to this work
3Joint senior authors
4Department of Endocrinology, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Fudan University, Shanghai, China

Tóm tắt

SUMMARY The 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. A 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). So 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. Transfection 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. Eleven 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. The 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.

Từ khóa


Tài liệu tham khảo

10.1161/hc0302.102143

10.1016/j.jacc.2005.06.007

10.1161/01.RES.0000232352.90786.fa

10.1016/j.pharmthera.2005.10.008

10.2337/diacare.18.5.708

10.1016/S0008-6363(00)00228-5

10.1002/path.1711660308

10.1016/0092-8674(93)90529-Y

10.1038/35002607

10.1016/S0092-8674(04)00045-5

10.1161/CIRCRESAHA.107.153916

10.1038/nature02255

10.1038/nature03817

10.1016/S0092-8674(03)00231-9

10.1038/ng1725

10.1126/science.1109020

10.1126/science.1091903

10.1158/0008-5472.CAN-05-1783

10.1182/blood-2006-01-012369

10.1007/BF00571939

10.1161/01.CIR.97.21.2175

10.1038/sj.cr.7290322

Ning YX, 2005, Study on the cytological characteristics of rat myocardium microvascular endothelial cells in culture of primary passage by microarray, Chin. J. Pathophysiol, 21, 2295

Janssen U, 1999, Rodent models of nephropathy associated with type II diabetes, J. Nephrol, 12, 159

Janssen U, 2004, The quest for a model of type II diabetes with nephropathy: The Goto Kakizaki rat, J. Nephrol, 17, 769

10.1038/nature03076

10.1073/pnas.0510928103

10.1016/S0076-6879(07)27006-5

10.1016/S0092-8674(03)01018-3

10.1371/journal.pbio.0020363

10.1038/ng1536

10.1016/j.cell.2004.12.035

10.1161/01.ATV.0000105902.89459.09

10.1038/70963

10.1016/j.ymthe.2003.10.003

10.2337/diabetes.54.1.175

10.1074/jbc.M304498200

10.1074/jbc.M800731200

Thông tin
Thông tin xuất bản

Clinical and Experimental Pharmacology and Physiology

Tập 36 Số 2

181-188

Thông tin tác giả