Renal medullary microRNAs in Dahl salt-sensitive rats: miR-29b regulates several collagens and related genes. Hypertension 2010 Apr;55(4):974-82
Date
03/03/2010Pubmed ID
20194304Pubmed Central ID
PMC2862728DOI
10.1161/HYPERTENSIONAHA.109.144428Scopus ID
2-s2.0-77950500403 (requires institutional sign-in at Scopus site) 227 CitationsAbstract
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-13(BN) rats but not in SS rats. miR-29b was predicted to regulate 20 collagen genes, matrix metalloproteinase 2 (Mmp2), integrin beta1 (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.
Author List
Liu Y, Taylor NE, Lu L, Usa K, Cowley AW Jr, Ferreri NR, Yeo NC, Liang MAuthor
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Blood Pressure
Blotting, Western
Collagen
Gene Expression Profiling
Integrin beta1
Kidney Medulla
Matrix Metalloproteinase 2
MicroRNAs
RNA, Messenger
Rats
Rats, Inbred Dahl
Reverse Transcriptase Polymerase Chain Reaction
Sodium Chloride, Dietary
