ArticleThe American journal of pathology2022
Dedicator of Cytokinesis 2 (DOCK2) Deficiency Attenuates Lung Injury Associated with Chronic High-Fat and High-Fructose Diet-Induced Obesity.
Article in The American journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- BRD4 Mediates Transforming Growth Factor-β-Induced Smooth Muscle Cell Differentiation from Mesenchymal Progenitor Cells.International journal of molecular sciences · 2025Article
- Associations of metabolic syndrome with lung function decline and clinical respiratory outcomes: the NHLBI Pooled Cohort Study.ERJ open research · 2025Article
- Obesity promotes ARDS by modulating ceramide transfer protein-ceramide pathway and exacerbating oxidative stress/apoptosis in alveolar macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Inhibition of RAC1 activator DOCK2 ameliorates cholestatic liver injury via regulating macrophage polarisation and hepatic stellate cell activation.Biology direct · 2025Article
- Silencing DOCK2 Attenuates Cardiac Fibrosis Following Myocardial Infarction in Mice Via Targeting PI3K/Akt and Wnt/β-Catenin Pathways.Journal of cardiovascular translational research · 2024Article
- DOCK2 Promotes Atherosclerosis by Mediating the Endothelial Cell Inflammatory Response.The American journal of pathology · 2024Article
- Effects of Low-Carbohydrate and Low-Fat Diets on Morbidity and Mortality of COPD.International journal of chronic obstructive pulmonary disease · 2024Article
- Pulmonary Fibrosis and Diabetes Mellitus: Two coins with the same face.Archives of internal medicine research · 2024Article
- MARCH8 downregulation modulates profibrotic responses including myofibroblast differentiation.American journal of physiology. Cell physiology · 2023Article
- Linking Adiposity to Interstitial Lung Disease: The Role of the Dysfunctional Adipocyte and Inflammation.Cells · 2023Review
- PFKFB3 Inhibits Fructose Metabolism in Pulmonary Microvascular Endothelial Cells.American journal of respiratory cell and molecular biology · 2023Article
- High-Fat Diet Related Lung Fibrosis-Epigenetic Regulation Matters.Biomolecules · 2023Review
- Inhibition of fatty acid synthase protects obese mice from acute lung injury via ameliorating lung endothelial dysfunction.Respiratory research · 2023Article
- DOCK2 contributes to pulmonary fibrosis by promoting lung fibroblast to myofibroblast transition.American journal of physiology. Cell physiology · 2022Article
- Insights from DOCK2 in cell function and pathophysiology.Frontiers in molecular biosciences · 2022Review
- Obesity and the Development of Lung Fibrosis.Frontiers in pharmacology · 2021Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Obesity is a major risk factor for lung disease development. However, little is known about the impact of chronic high-fat and high-fructose (HFHF) diet-induced obesity on lung inflammation and subsequent pulmonary fibrosis. Herein we hypothesized that dedicator of cytokinesis 2 (DOCK2) promotes a proinflammatory phenotype of lung fibroblasts (LFs) to elicit lung injury and fibrosis in chronic HFHF diet-induced obesity. An HFHF diet for 20 weeks induced lung inflammation and profibrotic changes in wild-type C57BL/6 mice. CD68 and monocyte chemoattractant protein-1 (MCP-1) expression were notably increased in the lungs of wild-type mice fed an HFHF diet. An HFHF diet further increased lung DOCK2 expression that co-localized with fibroblast-specific protein 1, suggesting a role of DOCK2 in regulating proinflammatory phenotype of LFs. Importantly, DOCK2 knockout protected mice from lung inflammation and fibrosis induced by a HFHF diet. In primary human LFs, tumor necrosis factor-α (TNF-α) and IL-1β induced DOCK2 expression concurrent with MCP-1, IL-6, and matrix metallopeptidase 2. DOCK2 knockdown suppressed TNF-α-induced expression of these molecules and activation of phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways, suggesting a mechanism of DOCK2-mediated proinflammatory and profibrotic changes in human LFs. Taken together, these findings reveal a previously unrecognized role of DOCK2 in regulating proinflammatory phenotype of LFs, potentiation of lung inflammation, and pulmonary fibrosis in chronic HFHF diet-caused obesity.
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Registered trials
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