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Loss of β-catenin in resident cardiac fibroblasts attenuates fibrosis induced by pressure overload in mice
- Source :
- Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017), Nature Communications
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- Cardiac fibrosis is characterized by excessive extracellular matrix deposition that contributes to compromised cardiac function and potentially heart failure. Cardiac pressure overload resulting from trans-aortic constriction in mice leads to cardiac fibrosis and increased Wnt/β-catenin signaling in cardiac fibroblasts. Here, we conditionally induce β-catenin loss of function in resident cardiac fibroblasts using Tcf21 MerCreMer or in activated cardiac fibroblasts using periostin (Postn)MerCreMer. We show that β-catenin loss of function in cardiac fibroblasts after trans-aortic constriction significantly preserves cardiac function, and reduces interstitial fibrosis but does not alter the numbers of activated or differentiated cardiac fibroblasts in vivo. However, β-catenin is specifically required in resident cardiac fibroblasts for fibrotic excessive extracellular matrix gene expression and binds Col3a1 and Postn gene sequences in cultured cardiac fibroblasts after induction of Wnt signaling. Moreover, cardiomyocyte hypertrophy is blunted with cardiac fibroblast-specific loss of β-catenin after trans-aortic constriction in vivo. Thus, Wnt/β-catenin signaling in resident cardiac fibroblasts is required for excessive extracellular matrix gene expression and collagen deposition after trans-aortic constriction.<br />Understanding the mechanisms causing cardiac fibrosis is key to prevention and therapy development of many heart diseases. Here, the authors show that Wnt/β-catenin signaling in resident cardiac fibroblasts is required for deposition of fibrotic extracellular matrix and the regulation of cardiomyocyte hypertrophy in a mouse model of heart fibrosis.
- Subjects :
- 0301 basic medicine
Cardiac function curve
Male
Heart Diseases
Cardiac fibrosis
Science
General Physics and Astronomy
030204 cardiovascular system & hematology
Periostin
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Extracellular matrix
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
medicine
Basic Helix-Loop-Helix Transcription Factors
Pressure
Animals
Humans
lcsh:Science
Wnt Signaling Pathway
Aorta
beta Catenin
Pressure overload
Mice, Knockout
Multidisciplinary
Wnt signaling pathway
Heart
General Chemistry
Anatomy
Fibroblasts
medicine.disease
3. Good health
Cell biology
Extracellular Matrix
030104 developmental biology
Heart failure
cardiovascular system
Female
lcsh:Q
Collagen
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....c5815270d7cc8e7e83d40743376a6b42