ArticleThe American journal of pathology2013
The c-Rel subunit of NF-κB regulates epidermal homeostasis and promotes skin fibrosis in mice.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 39 citations in OpenAlex.
- Structural alterations in PPP1R13L, SAE1, ATP5A1 and PCK2 disrupt NF-κB signalling and mitochondrial metabolism in primary dermal fibroblasts in systemic sclerosis.Rheumatology (Oxford, England) · 2026Article
- NF-κB-c-Rel in psoriasis: genetic susceptibility, immunopathogenic circuits, and emerging therapeutic opportunities.Frontiers in immunology · 2026Review
- Endothelial c-REL orchestrates atherosclerosis at regions of disturbed flow through crosstalk with TXNIP-p38 and non-canonical NF-κB pathways.Cardiovascular research · 2025Article
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders.Biomedicines · 2024Review
- Exploring the Functions of Mutant p53 throughCurrent issues in molecular biology · 2024Article
- Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis.Frontiers in genetics · 2023Article
- NF-кB c-Rel modulates pre-fibrotic changes in human fibroblasts.Archives of dermatological research · 2022Article
- Article
- Association of GTF2I, NFKB1, and TYK2 Regional Polymorphisms With Systemic Sclerosis in a Chinese Han Population.Frontiers in immunology · 2021Article
- c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.Nature metabolism · 2020Article
- NF-κB c-Rel Dictates the Inflammatory Threshold by Acting as a Transcriptional Repressor.iScience · 2020Article
- Deletion of NFKB1 enhances canonical NF-κB signaling and increases macrophage and myofibroblast content during tendon healing.Scientific reports · 2019Article
- Therapeutic strategies for enhancing angiogenesis in wound healing.Advanced drug delivery reviews · 2019Review
- RGC32 Promotes Bleomycin-Induced Systemic Sclerosis in a Murine Disease Model by Modulating Classically Activated Macrophage Function.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The Direct and Indirect Roles of NF-κB in Cancer: Lessons from Oncogenic Fusion Proteins and Knock-in Mice.Biomedicines · 2018Review
- Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.Rheumatology (Oxford, England) · 2017Article
- Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences.International journal of molecular sciences · 2017Review
- A MicroRNA that Regulates TLR-Mediated Fibrosis.International journal of molecular sciences · 2016Article
- c-Rel Regulates Inscuteable Gene Expression during Mouse Embryonic Stem Cell Differentiation.The Journal of biological chemistry · 2016Article
- c-Rel and its many roles in cancer: an old story with new twists.British journal of cancer · 2016Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The five subunits of transcription factor NF-κB have distinct biological functions. NF-κB signaling is important for skin homeostasis and aging, but the contribution of individual subunits to normal skin biology and disease is unclear. Immunohistochemical analysis of the p50 and c-Rel subunits within lesional psoriatic and systemic sclerosis skin revealed abnormal epidermal expression patterns, compared with healthy skin, but RelA distribution was unaltered. The skin of Nfkb1(-/-) and c-Rel(-/-) mice is structurally normal, but epidermal thickness and proliferation are significantly reduced, compared with wild-type mice. We show that the primary defect in both Nfkb1(-/-) and c-Rel(-/-) mice is within keratinocytes that display reduced proliferation both in vitro and in vivo. However, both genotypes can respond to proliferative stress, with 12-O-tetradecanoylphorbol-13-acetate-induced epidermal hyperproliferation and closure rates of full-thickness skin wounds being equivalent to those of wild-type controls. In a model of bleomycin-induced skin fibrosis, Nfkb1(-/-) and c-Rel(-/-) mice displayed opposite phenotypes, with c-Rel(-/-) mice being protected and Nfkb1(-/-) developing more fibrosis than wild-type mice. Taken together, our data reveal a role for p50 and c-Rel in regulating epidermal proliferation and homeostasis and a profibrogenic role for c-Rel in the skin, and identify a link between epidermal c-Rel expression and systemic sclerosis. Modulating the actions of these subunits could be beneficial for treating hyperproliferative or fibrogenic diseases of the skin.
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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.