ArticleThe Journal of biological chemistry2014
Modulation of the mevalonate pathway by akt regulates macrophage survival and development of pulmonary fibrosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05976217 (Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis), which is not on this map. Cited by 30 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.
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.
Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis
Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Mechanosignaling promotes macrophage apoptosis resistance in pulmonary fibrosisbioRxiv : the preprint server for biology · 2026Article
- Dissecting the Phospho-Regulatory Landscape of Protein Kinase N1 (PKN1) and Its Downstream Signaling: Functional Insights into the Activity-Dependent and Disease-Relevant Phosphosites.International journal of molecular sciences · 2026Article
- A system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications.Frontiers in bioinformatics · 2026Article
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
- The role of protein prenylation inhibition through targeting FPPS by zoledronic acid in the prevention of renal fibrosis in rats.Scientific reports · 2024Article
- The impact ofFrontiers in immunology · 2024Review
- The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease.Biology · 2023Review
- Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.International journal of molecular sciences · 2023Article
- Farnesyl diphosphate synthase regulated endothelial proliferation and autophagy during rat pulmonary arterial hypertension induced by monocrotaline.Molecular medicine (Cambridge, Mass.) · 2022Article
- Mutant p53, the Mevalonate Pathway and the Tumor Microenvironment Regulate Tumor Response to Statin Therapy.Cancers · 2022Review
- Zoledronic Acid Targeting of the Mevalonate Pathway Causes Reduced Cell Recruitment and Attenuates Pulmonary Fibrosis.Frontiers in pharmacology · 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
- Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- Cadmium-mediated lung injury is exacerbated by the persistence of classically activated macrophages.The Journal of biological chemistry · 2020Article
- PM014 attenuates radiation-induced pulmonary fibrosis via regulating NF-kB and TGF-b1/NOX4 pathways.Scientific reports · 2020Article
- Mitochondrial quality control in pulmonary fibrosis.Redox biology · 2020Review
- Predicting the effect of 5-fluorouracil-based adjuvant chemotherapy on colorectal cancer recurrence: A model using gene expression profiles.Cancer medicine · 2020Article
- TIM-4 interference in Kupffer cells against CCL4-induced liver fibrosis by mediating Akt1/Mitophagy signalling pathway.Cell proliferation · 2020Article
- Increased flux through the mevalonate pathway mediates fibrotic repair without injury.The Journal of clinical investigation · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase B (Akt) is a key effector of multiple cellular processes, including cell survival. Akt, a serine/threonine kinase, is known to increase cell survival by regulation of the intrinsic pathway for apoptosis. In this study, we found that Akt modulated the mevalonate pathway, which is also linked to cell survival, by increasing Rho GTPase activation. Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser(96). This phosphorylation in macrophages increased activation of Rac1, which enhanced macrophage survival because mutation of MDD (MDDS96A) induced apoptosis. Akt-mediated activation in macrophages was specific for Rac1 because Akt did not increase activity of other Rho GTP-binding proteins. The relationship between Akt and Rac1 was biologically relevant because Akt(+/-) mice had significantly less active Rac1 in alveolar macrophages, and macrophages from Akt(+/-) mice had an increase in active caspase-9 and -3. More importantly, Akt(+/-) mice were significantly protected from the development of pulmonary fibrosis, suggesting that macrophage survival is associated with the fibrotic phenotype. These observations for the first time suggest that Akt plays a critical role in the development and progression of pulmonary fibrosis by enhancing macrophage survival via modulation of the mevalonate pathway.
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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.