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http://purl.uniprot.org/citations/24006456http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24006456http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

MicroRNAs (miRNAs), in particular miR-29b and miR-30c, have been implicated as important regulators of cardiac fibrosis.

Objective

To perform a proteomics comparison of miRNA effects on extracellular matrix secretion by cardiac fibroblasts.

Methods and results

Mouse cardiac fibroblasts were transfected with pre-/anti-miR of miR-29b and miR-30c, and their conditioned medium was analyzed by mass spectrometry. miR-29b targeted a cadre of proteins involved in fibrosis, including multiple collagens, matrix metalloproteinases, and leukemia inhibitory factor, insulin-like growth factor 1, and pentraxin 3, 3 predicted targets of miR-29b. miR-29b also attenuated the cardiac fibroblast response to transforming growth factor-β. In contrast, miR-30c had little effect on extracellular matrix production but opposite effects regarding leukemia inhibitory factor and insulin-like growth factor 1. Both miRNAs indirectly affected cardiac myocytes. On transfection with pre-miR-29b, the conditioned medium of cardiac fibroblasts lost its ability to support adhesion of rat ventricular myocytes and led to a significant reduction of cardiac myocyte proteins (α-actinin, cardiac myosin-binding protein C, and cardiac troponin I). Similarly, cardiomyocytes derived from mouse embryonic stem cells atrophied under pre-miR-29 conditioned medium, whereas pre-miR-30c conditioned medium had a prohypertrophic effect. Levels of miR-29a, miR-29c, and miR-30c, but not miR-29b, were significantly reduced in a mouse model of pathological but not physiological hypertrophy. Treatment with antagomiRs to miR-29b induced excess fibrosis after aortic constriction without overt deterioration in cardiac function.

Conclusions

Our proteomic analysis revealed novel molecular targets of miRNAs that are linked to a fibrogenic cardiac phenotype. Such comprehensive screening methods are essential to define the concerted actions of miRNAs in cardiovascular disease."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.113.302400"xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Dong X."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Lu R."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Yin X."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Didangelos A."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Mayr M."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Shah A.M."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Mayr U."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Zampetaki A."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Zimmermann W.H."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Barallobre-Barreiro J."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Drozdov I."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Sur S."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Cuello F."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Langley S.R."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Abonnenc M."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Nabeebaccus A.A."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/author"Stathopoulou K."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/pages"1138-1147"xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/title"Extracellular matrix secretion by cardiac fibroblasts: role of microRNA-29b and microRNA-30c."xsd:string
http://purl.uniprot.org/citations/24006456http://purl.uniprot.org/core/volume"113"xsd:string
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