ArticleAnnals of the rheumatic diseases2014
A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses.
Article in Annals of the rheumatic diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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.
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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility.Arthritis research & therapy · 2014Pooled it
- Network pharmacology and in vivo experimental analysis for validating the antifibrotic potential of Punica granatum leaves against skin scleroderma: the role of oxidative stress, inflammation and TGF-β1/Snail 1/p-Smad 3 signaling pathway.Inflammopharmacology · 2026Article
- The signaling pathway of PPAR-γ and its protective role in various diseases.Caspian journal of internal medicine · 2026Review
- The crosstalk between autophagy and ferroptosis in pulmonary fibrosis.Journal of biomedical research · 2025Article
- A Potential Role of Adropin in Inflammatory Rheumatic Diseases-What Do We Know So Far?Biomedicines · 2025Review
- Article
- Aging and homeostasis of the hypodermis in the age-related deterioration of skin function.Cell death & disease · 2024Review
- A cysteine proteinase inhibitor ALLN alleviates bleomycin-induced skin and lung fibrosis.Arthritis research & therapy · 2023Article
- Anti-fibrotic effect of ciglitazone in HRV-induced airway remodelling cell model.Journal of cellular and molecular medicine · 2023Article
- Perspective to precision medicine in scleroderma.Frontiers in immunology · 2023Article
- The compound LG283 inhibits bleomycin-induced skin fibrosis via antagonizing TGF-β signaling.Arthritis research & therapy · 2022Article
- Involvement of FoxO1, Sp1, and Nrf2 in Upregulation of Negative Regulator of ROS by 15d-PGJNeurotoxicity research · 2022Article
- A broad look into the future of systemic sclerosis.Therapeutic advances in musculoskeletal disease · 2022Review
- The role of antifibrotics in the treatment of rheumatoid arthritis-associated interstitial lung disease.Therapeutic advances in musculoskeletal disease · 2022Review
- Upcoming treatments for morphea.Immunity, inflammation and disease · 2021Review
- Updates on genetics in systemic sclerosis.Inflammation and regeneration · 2021Review
- The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review.Journal of autoimmunity · 2020Review
- Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Therapeutic potential of PPARγ natural agonists in liver diseases.Journal of cellular and molecular medicine · 2020Review
- The role and function of PPARγ in bladder cancer.Journal of Cancer · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundPersistent fibroblast activation initiated by transforming growth factor β (TGF-β) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents a potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exerts potent fibrotic activity. The synthetic oleanane triterpenoid, 2-cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO), is a PPAR-γ agonist with potential effects on TGF-β signalling and dermal fibrosis.
objectiveTo examine the modulation of fibrogenesis by CDDO in explanted fibroblasts, skin organ cultures and murine models of scleroderma. MATERIAL AND
methodsThe effects of CDDO on experimental fibrosis induced by bleomycin injection or by overexpression of constitutively active type I TGF-β receptor (TgfbR1ca) were evaluated. Modulation of fibrotic gene expression was examined in human skin organ cultures. To delineate the mechanisms underlying the antifibrotic effects of CDDO, explanted skin fibroblasts cultured in two-dimensional monolayers or in three-dimensional full-thickness human skin equivalents were studied.
resultsCDDO significantly ameliorated dermal fibrosis in two complementary mouse models of scleroderma, as well as in human skin organ cultures and in three-dimensional human skin equivalents. In two-dimensional monolayer cultures of explanted normal fibroblasts, CDDO abrogated fibrogenic responses induced by TGF-β. These CDDO effects occurred via disruption of Smad-dependent transcription and were associated with inhibition of Akt activation. In scleroderma fibroblasts, CDDO attenuated the elevated synthesis of collagen. Remarkably, the in vitro antifibrotic effects of CDDO were independent of PPAR-γ.
conclusionsThe PPAR-γ agonist triterpenoid CDDO attenuates fibrogenesis by antagonistically targeting canonical TGF-β/Smad and Akt signalling in a PPAR-γ-independent manner. These findings identify this synthetic triterpenoid as a potential new therapy for the control of fibrosis.
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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.