ArticleThe Journal of clinical investigation2019
Increased flux through the mevalonate pathway mediates fibrotic repair without injury.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Mechanosignaling promotes macrophage apoptosis resistance in pulmonary fibrosisbioRxiv : the preprint server for biology · 2026Article
- Vitamin D receptor suppresses pulmonary fibroblast activation by downregulating the TGF-β1/Smad signaling pathway.Histochemistry and cell biology · 2026Article
- Immunomodulatory Effects of Nintedanib on Human Blood Monocytes/Macrophages from Patients with Idiopathic Pulmonary Fibrosis.Biomolecules · 2026Article
- Simvastatin Alleviates ConA-Induced Autoimmune Hepatitis by Inhibiting CD4Inflammation · 2026Article
- Anti-inflammatory effect of fluvastatin on polarized macrophages and its dependence on the mevalonate pathway.Scientific reports · 2025Article
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
- Serine metabolism in macrophage polarization.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Myeloid Heterogeneity Mediates Acute Exacerbations of Pulmonary Fibrosis.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Review
- Article
- Mitochondrial quality control in lung diseases: current research and future directions.Frontiers in physiology · 2023Review
- [Advances in gut microbiomes and immunology of IgG4-related hepatobiliary and pancreatic diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Review
- Article
- Progress of Statin Therapy in the Treatment of Idiopathic Pulmonary Fibrosis.Oxidative medicine and cellular longevity · 2022Review
- Zoledronic Acid Targeting of the Mevalonate Pathway Causes Reduced Cell Recruitment and Attenuates Pulmonary Fibrosis.Frontiers in pharmacology · 2022Article
- Targeting Cpt1a-Bcl-2 interaction modulates apoptosis resistance and fibrotic remodeling.Cell death and differentiation · 2022Article
- NOX4 regulates macrophage apoptosis resistance to induce fibrotic progression.The Journal of biological chemistry · 2021Article
- Post-translational regulation of PGC-1α modulates fibrotic repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Exploring the Role of ATP-Citrate Lyase in the Immune System.Frontiers in immunology · 2021Review
- Cadmium-mediated lung injury is exacerbated by the persistence of classically activated macrophages.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Macrophages are important in mounting an innate immune response to injury as well as in repair of injury. Gene expression of Rho proteins is known to be increased in fibrotic models; however, the role of these proteins in idiopathic pulmonary fibrosis (IPF) is not known. Here, we show that BAL cells from patients with IPF have a profibrotic phenotype secondary to increased activation of the small GTPase Rac1. Rac1 activation requires a posttranslational modification, geranylgeranylation, of the C-terminal cysteine residue. We found that by supplying more substrate for geranylgeranylation, Rac1 activation was substantially increased, resulting in profibrotic polarization by increasing flux through the mevalonate pathway. The increased flux was secondary to greater levels of acetyl-CoA from metabolic reprogramming to β oxidation. The polarization mediated fibrotic repair in the absence of injury by enhancing macrophage/fibroblast signaling. These observations suggest that targeting the mevalonate pathway may abrogate the role of macrophages in dysregulated fibrotic repair.
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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.