ArticleBiochimica et biophysica acta. Molecular cell research2020
The role of Smad2 and Smad3 in regulating homeostatic functions of fibroblasts in vitro and in adult mice.
Article in Biochimica et biophysica acta. Molecular cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Antagonistic SMAD2/3 control of TIMP-1, VEGF-A, and hypoxia signaling in myofibroblasts shapes histotype-specific angiogenesis in lung cancer.Cell death & disease · 2026Article
- Bladder neck contracture: incidence, mechanisms, and therapeutic advances.Annals of medicine and surgery (2012) · 2025Review
- Fibroblast-specific TGF-β signaling mediates cardiac dysfunction, fibrosis, and hypertrophy in obese diabetic mice.Cardiovascular research · 2024Article
- Functional analysis of cell lines derived from SMAD3-related Loeys-Dietz syndrome patients provides insights into genotype-phenotype relation.Human molecular genetics · 2024Article
- Hitting the Target! Challenges and Opportunities for TGF-β Inhibition for the Treatment of Cardiac fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix.JCI insight · 2024Article
- Carbonic Anhydrase 3 is required for cardiac repair post myocardial infarction via Smad7-Smad2/3 signaling pathway.International journal of biological sciences · 2024Article
- The epithelium takes the stage in asthma and inflammatory bowel diseases.Frontiers in cell and developmental biology · 2024Review
- Deep learning untangles the resistance mechanism of p53 reactivator in lung cancer cells.iScience · 2023Article
- Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.Cellular & molecular biology letters · 2023Article
- The role of SMAD signaling in hypertrophic obstructive cardiomyopathy: an immunohistopathological study in pediatric and adult patients.Scientific reports · 2023Article
- Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis.Rheumatology (Oxford, England) · 2023Article
- ALK5 Inhibition of Subconjunctival Scarring From Glaucoma Surgery: Effects of SB-431542 Compared to Mitomycin C in Human Tenon's Capsule Fibroblasts.Translational vision science & technology · 2023Article
- Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy.Frontiers in endocrinology · 2023Review
- Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.Frontiers in pharmacology · 2023Review
- Transforming growth factor-β in myocardial disease.Nature reviews. Cardiology · 2022Review
- Smad-dependent pathways in the infarcted and failing heart.Current opinion in pharmacology · 2022Review
- Review
- Signaling cascades in the failing heart and emerging therapeutic strategies.Signal transduction and targeted therapy · 2022Review
- Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The heart contains an abundant fibroblast population that may play a role in homeostasis, by maintaining the extracellular matrix (ECM) network, by regulating electrical impulse conduction, and by supporting survival and function of cardiomyocytes and vascular cells. Despite an explosion in our understanding of the role of fibroblasts in cardiac injury, the homeostatic functions of resident fibroblasts in adult hearts remain understudied. TGF-β-mediated signaling through the receptor-activated Smads, Smad2 and Smad3 critically regulates fibroblast function. We hypothesized that baseline expression of Smad2/3 in fibroblasts may play an important role in cardiac homeostasis. Smad2 and Smad3 were constitutively expressed in normal mouse hearts and in cardiac fibroblasts. In cultured cardiac fibroblasts, Smad2 and Smad3 played distinct roles in regulation of baseline ECM gene synthesis. Smad3 knockdown attenuated collagen I, collagen IV and fibronectin mRNA synthesis and reduced expression of the matricellular protein thrombospondin-1. Smad2 knockdown on the other hand attenuated expression of collagen V mRNA and reduced synthesis of fibronectin, periostin and versican. In vivo, inducible fibroblast-specific Smad2 knockout mice and fibroblast-specific Smad3 knockout mice had normal heart rate, preserved cardiac geometry, ventricular systolic and diastolic function, and normal myocardial structure. Fibroblast-specific Smad3, but not Smad2 loss modestly but significantly reduced collagen content. Our findings suggest that fibroblast-specific Smad3, but not Smad2, may play a role in regulation of baseline collagen synthesis in adult hearts. However, at least short term, these changes do not have any impact on homeostatic cardiac function.
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