ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Aberrant differentiation of fibroblast progenitors contributes to fibrosis in the aged murine heart: role of elevated circulating insulin levels.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Hybrid hydrogel-extracellular matrix scaffolds identify biochemical and mechanical signatures of cardiac ageing.Nature materials · 2025Article
- Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential.The journal of cardiovascular aging · 2024Article
- The Senescent Heart-"Age Doth Wither Its Infinite Variety".International journal of molecular sciences · 2024Review
- Sex-specific phenotypes in the aging mouse heart and consequences for chronic fibrosis.American journal of physiology. Heart and circulatory physiology · 2022Article
- Cleavage stimulating factor 64 depletion mitigates cardiac fibrosis through alternative polyadenylation.Biochemical and biophysical research communications · 2022Article
- Dysregulated Epicardial Adipose Tissue as a Risk Factor and Potential Therapeutic Target of Heart Failure with Preserved Ejection Fraction in Diabetes.Biomolecules · 2022Review
- Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities.Advanced drug delivery reviews · 2021Review
- Heart failure with preserved ejection fraction based on aging and comorbidities.Journal of translational medicine · 2021Review
- Treatment with a DC-SIGN ligand reduces macrophage polarization and diastolic dysfunction in the aging female but not male mouse hearts.GeroScience · 2021Article
- Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway.Circulation research · 2021Article
- Mechanosensing dysregulation in the fibroblast: A hallmark of the aging heart.Ageing research reviews · 2020Review
- IL-18/IL-18R1 promotes circulating fibrocyte differentiation in the aging population.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Review
- Differential Gender-Dependent Patterns of Cardiac Fibrosis and Fibroblast Phenotypes in Aging Mice.Oxidative medicine and cellular longevity · 2020Article
- Disease-treatment interactions in the management of patients with obesity and diabetes who have atrial fibrillation: the potential mediating influence of epicardial adipose tissue.Cardiovascular diabetology · 2019Article
- Changes in cardiac resident fibroblast physiology and phenotype in aging.American journal of physiology. Heart and circulatory physiology · 2018Review
- Aicar treatment reduces interstitial fibrosis in aging mice: Suppression of the inflammatory fibroblast.Journal of molecular and cellular cardiology · 2017Article
- Dissecting the role of myeloid and mesenchymal fibroblasts in age-dependent cardiac fibrosis.Basic research in cardiology · 2017Article
- Antioxidant and Antifibrotic Effect of a Herbal FormulationOxidative medicine and cellular longevity · 2017Article
- Insulin Cannot Induce Adipogenic Differentiation in Primary Cardiac Cultures.The International journal of angiology : official publication of the International College of Angiology, Inc · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
With age, the collagen content of the heart increases, leading to interstitial fibrosis. We have shown that CD44(pos) fibroblasts derived from aged murine hearts display reduced responsiveness to TGF-β but, paradoxically, have increased collagen expression in vivo and in vitro. We postulated that this phenomenon was due to the defect in mesenchymal stem cell (MSC) differentiation in a setting of elevated circulating insulin levels and production that we observed in aging mice. We discovered that cultured fibroblasts derived from aged but not young cardiac MSCs of nonhematopoietic lineage displayed increased basal and insulin-induced (1 nM) collagen expression (2-fold), accompanied by increased farnesyltransferase (FTase) and Erk activities. In a quest for a possible mechanism, we found that a chronic pathophysiologic insulin concentration (1 nM) caused abnormal fibroblast differentiation of MSCs isolated from young hearts. Fibroblasts derived from these MSCs responded to insulin by elevating collagen expression as seen in untreated aged fibroblast cultures, suggesting a causal link between increased insulin levels and defective MSC responses. Here we report an insulin-dependent pathway that specifically targets collagen type I transcriptional activation leading to a unique mechanism of fibrosis that is TGF-β and inflammation-independent in the aged heart.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.