ArticleOncotarget2016
SIRT3 is attenuated in systemic sclerosis skin and lungs, and its pharmacologic activation mitigates organ fibrosis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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
71 citing papers in PubMed, 106 citations in OpenAlex.
- An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).International journal of molecular medicine · 2026Review
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- SZC-6 Promotes Diabetic Wound Healing in Mice by Modulating the M1/M2 Macrophage Ratio and Inhibiting the MyD88/NF-χB Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Sirtuin family in lung adenocarcinoma.Discover oncology · 2025Review
- Resveratrol ameliorates pathological fibrosis of the myodural bridge by regulating the SIRT3/TGF-β1/Smad pathway.Heliyon · 2024Article
- Review
- Pulmonary Fibrosis and Diabetes Mellitus: Two coins with the same face.Archives of internal medicine research · 2024Article
- Research progress of SIRTs activator resveratrol and its derivatives in autoimmune diseases.Frontiers in immunology · 2024Review
- Heavy-chain antibody targeting of CD38 NADScientific reports · 2023Article
- Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism.Cell death & disease · 2023Article
- The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease.Biology · 2023Review
- Sirtuin3 confers protection against acute pulmonary embolism through anti-inflammation, and anti-oxidative stress, and anti-apoptosis properties: participation of the AMP-activated protein kinase/mammalian target of rapamycin pathway.Experimental animals · 2023Article
- Advances in cellular senescence in idiopathic pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2023Review
- The Molecular Mechanisms of Systemic Sclerosis-Associated Lung Fibrosis.International journal of molecular sciences · 2023Review
- Sirtuin family in autoimmune diseases.Frontiers in immunology · 2023Review
- The role of sirtuins in dermal fibroblast function.Frontiers in medicine · 2023Review
- SIRT3 activation promotes enteric neurons survival and differentiation.Scientific reports · 2022Article
- Age-related mechanisms in the context of rheumatic disease.Nature reviews. Rheumatology · 2022Review
- Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022Review
11 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
10 authors at 4 institutions in 1 country.
Funding
Abstract
Constitutive fibroblast activation is responsible for organ fibrosis in fibrotic disorders including systemic sclerosis (SSc), but the underlying mechanisms are not fully understood, and effective therapies are lacking. We investigated the expression of the mitochondrial deacetylase sirtuin 3 (SIRT3) and its modulation by hexafluoro, a novel fluorinated synthetic honokiol analogue, in the context of fibrosis. We find that augmenting cellular SIRT3 by forced expression in normal lung and skin fibroblasts, or by hexafluoro treatment, blocked intracellular TGF-ß signaling and fibrotic responses, and mitigated the activated phenotype of SSc fibroblasts. Moreover, hexafluoro attenuated mitochondrial and cytosolic reactive oxygen species (ROS) accumulation in TGF-β-treated fibroblasts. Remarkably, we found that the expression of SIRT3 was significantly reduced in SSc skin biopsies and explanted fibroblasts, and was suppressed by TGF-β treatment in normal fibroblasts. Moreover, tissue levels of acetylated MnSOD, a sensitive marker of reduced SIRT3 activity, were dramatically enhanced in lesional skin and lung biopsies from SSc patients. Mice treated with hexafluoro showed substantial attenuation of bleomycin-induced fibrosis in the lung and skin. Our findings reveal a cell-autonomous function for SIRT3 in modulating fibrotic responses, and demonstrate the ability of a novel pharmacological SIRT3 agonist to attenuate fibrosis in vitro and in vivo. In light of the impaired expression and activity of SIRT3 associated with organ fibrosis in SSc, pharmacological approaches for augmenting SIRT3 might have therapeutic potential.
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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.