ArticlePloS one2019
Yin/Yang expression of CCN family members: Transforming growth factor beta 1, via ALK5/FAK/MEK, induces CCN1 and CCN2, yet suppresses CCN3, expression in human dermal fibroblasts.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- CCN Proteins as Matricellular Regulators of Bone in Aging and Disease.Current osteoporosis reports · 2025Review
- Matricellular protein CCN1 promotes collagen alignment and scar integrity after myocardial infarction.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Evaluation of the Use of Cell Lines in Studies of Selenium-Dependent Glutathione Peroxidase 2 (GPX2) Involvement in Colorectal Cancer.Diseases (Basel, Switzerland) · 2024Article
- Elevated reactive aggression in forebrain-specificJournal of cell communication and signaling · 2024Article
- Review
- The advance of CCN3 in fibrosis.Journal of cell communication and signaling · 2023Review
- Back to the future: targeting the extracellular matrix to treat systemic sclerosis.Nature reviews. Rheumatology · 2023Review
- The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes.Frontiers in cardiovascular medicine · 2023Article
- Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration.International journal of molecular sciences · 2022Review
- Selective deletion of connective tissue growth factor attenuates experimentally-induced pulmonary fibrosis and pulmonary arterial hypertension.The international journal of biochemistry & cell biology · 2021Article
- Transient ACE (Angiotensin-Converting Enzyme) Inhibition Suppresses Future Fibrogenic Capacity and Heterogeneity of Cardiac Fibroblast Subpopulations.Hypertension (Dallas, Tex. : 1979) · 2021Article
- CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis.Journal of cell communication and signaling · 2021Review
- Verteporfin inhibits the persistent fibrotic phenotype of lesional scleroderma dermal fibroblasts.Journal of cell communication and signaling · 2021Article
- The Emerging Roles of CCN3 Protein in Immune-Related Diseases.Mediators of inflammation · 2021Review
- CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment.Frontiers in genetics · 2021Review
- Et tu, CCN1….Journal of cell communication and signaling · 2020Article
- Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification.JCI insight · 2020Article
- Conjunction junction, what's the function? CCN proteins as targets in fibrosis and cancers.American journal of physiology. Cell physiology · 2020Review
- Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The role of the microenvironment in driving connective tissue disease is being increasingly appreciated. Matricellular proteins of the CCN family are signaling modifiers that are secreted by cells into the extracellular matrix microenvironment where they have profound, context-dependent effects on organ development, homeostasis and disease. Indeed, CCN proteins are emergent targets for therapeutic intervention. Recent evidence suggests that, in vivo, CCN3 has effects opposing CCN2. Moreover, when CCN3 expression is high, CCN2 expression is low. That is, they appear to be regulated in a yin/yang fashion, leading to the hypothesis that the CCN2:CCN3 ratio is important to control tissue homeostasis. To begin to test the hypothesis that alterations in CCN2:CCN3 expression might be important in skin biology in vivo, we evaluated the relative ex vivo effects of the profibrotic protein TGFbeta1 on dermal fibroblasts on protein and RNA expression of CCN3 and CCN2, as well as the related protein CCN1. We also used signal transduction inhibitors to begin to identify the signal transduction pathways controlling the ability of fibroblasts to respond to TGFbeta1. As anticipated, CCN1 and CCN2 protein and mRNA were induced by TGFbeta1 in human dermal fibroblasts. This induction was blocked by TAK1, FAK, YAP1 and MEK inhibition. Conversely, TGFbeta1 suppressed CCN3 mRNA expression in a fashion insensitive to FAK, MEK, TAK1 or YAP1 inhibition. Unexpectedly, CCN3 protein was not detected in human dermal fibroblasts basally. These data suggest that, in dermal fibroblasts, the profibrotic protein TGFbeta1 has a divergent effect on CCN3 relative to CCN2 and CCN1, both at the mRNA and protein level. Given that the major source in skin in vivo of CCN proteins are fibroblasts, our data are consistent that alterations in CCN2/CCN1: CCN3 ratios in response to profibrotic agents such as TGFbeta1 may play a role in connective tissue pathologies including fibrosis.
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What OpenQuestion holds
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.