Renal Medullary MicroRNAs in Dahl Salt-Sensitive Rats miR-29b Regulates Several Collagens and Related Genes

被引:217
作者
Liu, Yong [1 ]
Taylor, Norman E. [1 ]
Lu, Limin [1 ,2 ]
Usa, Kristie [1 ]
Cowley, Allen W., Jr. [1 ]
Ferreri, Nicholas R. [3 ]
Yeo, Nan Cher [1 ]
Liang, Mingyu [1 ]
机构
[1] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
[2] Fudan Univ, Shanghai Med Coll, Dept Physiol & Pathophysiol, Shanghai 200433, Peoples R China
[3] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
基金
美国国家卫生研究院;
关键词
gene expression; renal injury; hypertension; extracellular matrix; kidney; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; MESSENGER-RNAS; HYPERTENSION; EXPRESSION; TARGET; KIDNEY; INJURY; MICROARRAY; MECHANISM; DELETION;
D O I
10.1161/HYPERTENSIONAHA.109.144428
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
MicroRNAs are endogenous repressors of gene expression. We examined microRNAs in the renal medulla of Dahl salt-sensitive rats and consomic SS-13(BN) rats. Salt-induced hypertension and renal injury in Dahl salt-sensitive rats, particularly medullary interstitial fibrosis, have been shown previously to be substantially attenuated in SS-13(BN) rats. Of 377 microRNAs examined, 5 were found to be differentially expressed between Dahl salt-sensitive rats and consomic SS-13(BN) rats receiving a high-salt diet. Real-time PCR analysis demonstrated that high-salt diets induced substantial upregulation of miR-29b in the renal medulla of SS-13BN rats but not in SS rats. miR-29b was predicted to regulate 20 collagen genes, matrix metalloproteinase 2 (Mmp2), integrin beta 1 (Itgb1), and other genes related to the extracellular matrix. Expression of 9 collagen genes and Mmp2 was upregulated by a high-salt diet in the renal medulla of SS rats, but not in SS-13(BN) rats, an expression pattern opposite to miR-29b. Knockdown of miR-29b in the kidneys of SS-13(BN) rats resulted in upregulation of several collagen genes. miR-29b reduced expression levels of several collagen genes and Itgb1 in cultured rat renal medullary epithelial cells. Moreover, miR-29b suppressed the activity of luciferase when the reporter gene was linked to a 3'-untranslated segment of collagen genes Col1a1, Col3a1, Col4a1, Col5a1, Col5a2, Col5a3, Col7a1, Col8a1, Mmp2, or Itgb1 but not Col12a1. The result demonstrated broad effects of miR-29b on a large number of collagens and genes related to the extracellular matrix and suggested involvement of miR-29b in the protection from renal medullary injury in SS-13(BN) rats. (Hypertension. 2010; 55: 974-982.)
引用
收藏
页码:974 / 982
页数:9
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