Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes

Autor: Vincent M. Christoffels, Cindy P. A. A. van Roomen, Esther E. Creemers, Ingeborg B. Hooijkaas, Hylja Heese, Lejla Medzikovic, Vivian de Waard, Pieter B. van Loenen, Carlie J.M. de Vries
Přispěvatelé: Medical Biochemistry, ACS - Heart failure & arrhythmias, Amsterdam Reproduction & Development (AR&D), Medical Biology, Cardiology, ACS - Diabetes & metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Atherosclerosis & ischemic syndromes
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Cardiac fibrosis
Mice
Knockout
ApoE
Heart Rupture
cardiomyocyte
030204 cardiovascular system & hematology
fibroblast
Extracellular matrix
lcsh:Chemistry
Mice
0302 clinical medicine
Fibrosis
Transforming Growth Factor beta
Nuclear Receptor Subfamily 4
Group A
Member 1
Myocytes
Cardiac
nuclear receptor
Myofibroblasts
lcsh:QH301-705.5
Spectroscopy
Cells
Cultured
Mice
Knockout
Ventricular Remodeling
Models
Cardiovascular
General Medicine
Computer Science Applications
Cell biology
Gene Knockdown Techniques
cardiovascular system
Intercellular Signaling Peptides and Proteins
Collagen
Cardiomyopathies
Nerve growth factor IB
cardiac
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Paracrine signalling
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Transforming growth factor β
business.industry
Myocardium
Organic Chemistry
Cardiac Rupture
fibrosis
Fibroblasts
medicine.disease
myofibroblast
Rats
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Heart failure
business
Transforming growth factor
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 1600, p 1600 (2021)
International journal of molecular sciences, 22(4):1600, 1-16. Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
Volume 22
Issue 4
ISSN: 1661-6596
1422-0067
Popis: Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis
however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.
Databáze: OpenAIRE
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