ArticleNature communications2014
Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- TGF-β-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis.The Journal of clinical investigation · 2020Trial
- An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- Emerging therapies for the treatment of systemic sclerosis.Nature reviews. Rheumatology · 2025Review
- Review
- Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states.Nature genetics · 2025Article
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- A Strong Dysregulated Myeloid Component in the Epigenetic Landscape of Systemic Sclerosis: An Integrated DNA Methylome and Transcriptome Analysis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases.Biomolecules · 2025Review
- Morroniside improves AngII-induced cardiac fibroblast proliferation, migration, and extracellular matrix deposition by blocking p38/JNK signaling pathway through the downregulation of KLF5.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Recent Insights into Cellular and Molecular Mechanisms of Defective Angiogenesis in Systemic Sclerosis.Biomedicines · 2024Review
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- Recent Insights into the Role of DNA Methylation and Histone Modifications in Systemic Sclerosis: A Scoping Review.Diagnostics (Basel, Switzerland) · 2024Article
- Tree shrews as a new animal model for systemic sclerosis research.Frontiers in immunology · 2024Article
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- Role of the transcription factor Fli-1 on the CXCL10/CXCR3 Axis.Frontiers in immunology · 2023Article
- The Involvement of Smooth Muscle, Striated Muscle, and the Myocardium in Scleroderma: A Review.International journal of molecular sciences · 2022Review
- Animal Models of Systemic Sclerosis: Using Nailfold Capillaroscopy as a Potential Tool to Evaluate Microcirculation and Microangiopathy: A Narrative Review.Life (Basel, Switzerland) · 2022Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Systemic sclerosis (SSc) is manifested by fibrosis, vasculopathy and immune dysregulation. So far, a unifying hypothesis underpinning these pathological events remains unknown. Given that SSc is a multifactorial disease caused by both genetic and environmental factors, we focus on the two transcription factors, which modulate the fibrotic reaction and are epigenetically suppressed in SSc dermal fibroblasts, Friend leukaemia integration 1 (Fli1) and Krüppel-like factor 5 (KLF5). In addition to the Fli1 silencing-dependent collagen induction, the simultaneous knockdown of Fli1 and KLF5 synergistically enhances expression of connective tissue growth factor. Notably, mice with double heterozygous deficiency of Klf5 and Fli1 mimicking the epigenetic phenotype of SSc skin spontaneously recapitulate all the three features of SSc, including fibrosis and vasculopathy of the skin and lung, B-cell activation and autoantibody production. These studies implicate the epigenetic downregulation of Fli1 and KLF5 as a central event triggering the pathogenic triad of SSc.
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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.