MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts (Nature, 2008, 456:980-984)

報告日期: 2009/05/05
報告時間: 17:05/17:55
報告學生: 藍昇輝
講評老師: 吳梨華
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980505-3.pdf

MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts

 

Thomas Thum. et al, Nature. 2008 Dec 18;456(7224):980-4. Epub 2008 Nov 30.

 

Speaker: 藍昇輝

Commentator: 吳梨華 老師

Time:2009/05/05 17:05~17:55

Place: Room 602

 

Abstract:

MicroRNA (miRNA) is a 20~23 nucleotide non-coding RNA. MiRNA inhibits target gene expression by binding the 3’UTR of mRNA, which blocks either transcription or translation of the target genes. Several miRNAs are dysregulated in various diseases including cancer, virus infection and cardiac disease. Previous studies have reported the miRNAs primarily expressed in cardiomyocte-related disease. The roles of heart disease-related miRNAs expression in other cell types are unclear. The authors reveal that miR-21 is specifically overexpressed in the fibroblasts of the failing heart. The miR-21 promotes ERK–MAP-kinase mediated cell survival through inhibition of sprouty homologue 1 (Spry1) in cardiac fibroblasts. The Spry1 is a highly conserved group of negative feedback loop modulators of growth factor-mediated mitogen-activated protein kinase (MAPK) activation. It suggests that miR-21 participates in fibroblast activity in myocardial disease. A chemically modified antisense oligonucleotide specific against miR-21 (antagomir-21) was injected into the mice subjected by transverse aortic constriction (TAC). The authors confirmed that miR-21 is a disease target in heart failure and miR-21 silencing can be used to prevent as well as treat in a cardiovascular disease setting. The authors also establish the therapeutic efficacy of microRNA therapeutic intervention of heart disease.

 

References:

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2.   Engelhardt, S., Hein, L., Wiesmann, F. & Lohse, M. J. Progressive hypertrophy and heart failure in b1-adrenergic receptor transgenic mice. Proc. Natl Acad. Sci. USA 96, 7059–7064 (1999).