Extracellular Matrix Secretion by Cardiac Fibroblasts: Role of MicroRNA-29b and MicroRNA-30c
2013 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Extracellular Matrix Secretion by Cardiac Fibroblasts: Role of MicroRNA-29b and MicroRNA-30c
Abonnenc, M.; Nabeebaccus, A. A.; Mayr, U.; Barallobre-Barreiro, J.; Dong, X.; Cuello, F. & Sur, S. et al. (2013)
Circulation Research, 113(10) pp. 1138-1147. DOI: https://doi.org/10.1161/CIRCRESAHA.113.302400
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Details
- Authors
- Abonnenc, Mélanie; Nabeebaccus, Adam A.; Mayr, Ursula; Barallobre-Barreiro, Javier; Dong, Xuebin; Cuello, Friederike; Sur, Sumon; Drozdov, Ignat; Langley, Sarah R.; Lu, Ruifang; Stathopoulou, Konstantina; Didangelos, Athanasios; Yin, Xiaoke; Zimmermann, Wolfram-Hubertus ; Shah, Ajay M.; Zampetaki, Anna; Mayr, Manuel
- Abstract
- 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-beta. 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 (a-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.
- Issue Date
- 2013
- Journal
- Circulation Research
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien - Working Group
- RG Zimmermann (Engineered Human Myocardium)
- ISSN
- 0009-7330; 1524-4571
- Language
- English