RESPIRATORY RESEARCH
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2024
·Vol. 25
·期 1
·1-13
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IF 4.7
Zhu Li,Wu Zhuhua,Liu Yingli,Ming Yue,Xie Pei,Jiang Miao,Qi Yong
Background Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear.Methods mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs.Results Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate.Conclusion Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.
研究领域:
呼吸系统疾病
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分子生物学
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细胞生物学
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内分泌学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Fructueux Modeste Amona,Xiaohan Chen,Shiqing Yang,Zhuoxuan Zhang,Zilu Liu,Yuenan Wang,Wenxin Chen,Rong Zhou,Xi Chen,Yipeng Pang,Jiabin Xu,Xingtang Fang
Background Acute infected wounds remain a major clinical challenge owing to persistent inflammation, oxidative stress, and impaired angiogenesis. While natural phenolic compounds, like ferulic acid (FA), have antioxidant properties, their role in coordinating wound repair across immune and vascular cells remains unclear. Purpose This study aims to elucidate the multi-modal mechanisms by which ferulic acid coordinates wound repair, focusing on its effects on redox regulation, immune modulation, and angiogenic activation in both cellular and murine models. Methods A combined in vitro and in vivo experimental approach was employed, using RAW264.7 macrophage and human umbilical vein endothelial cells (HUVECs) cultures, along with a full-thickness excisional wound model in mice, to investigate the therapeutic effects and molecular mechanisms of FA. Transcriptomic profiling and the role of Aconitate Decarboxylase 1 (ACOD1) were investigated via gene knockdown. Results FA effectively protected macrophages from oxidative injury by activating the Nrf2-Keap1 pathway, enhancing SOD/GPx activity, and suppressing NOX1 expression. In HUVECs under stress, FA restored proliferation, migration, and tube formation while increasing VEGF, TGF-β, and collagen I. Topically, FA accelerated wound healing in mice, reduced bacterial load, increased collagen deposition, and promoted angiogenesis. Transcriptomic analysis showed that FA reprograms the wound microenvironment by downregulating pro-inflammatory pathways (IL-17/TNF) and upregulating genes involved in extracellular matrix (ECM) and angiogenesis. ACOD1 was a required metabolic enzyme mediating FA's effects; its knockdown blocked FA’s antioxidant, mitochondrial, and angiogenic effects. Conclusion These findings elucidate a novel ACOD1-dependent pathway in which FA coordinates the resolution of oxidative stress and promotes tissue regeneration. FA emerges as a promising bioactive component for advanced wound-healing biomaterials. Download: Download high-res image (238KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Yizeng Fan,Weichao Dan,Yuzhao Wang,Zhiqiang Ma,Yanlin Jian,Tianjie Liu,Mengxing Li,Zixi Wang,Yi Wei,Bo Liu,Peng Ding,Yuzeshi Lei,Chendong Guo,Jin Zeng,Xiaolong Yan,Wenyi Wei,Lei Li
Itaconate is a metabolite catalyzed by cis- aconitate decarboxylase (ACOD1), which is mainly produced by activated macrophages and secreted into the extracellular environment to exert complex bioactivity. In the tumor microenvironment, itaconate is concentrated and induces an immunosuppressive response. However, whether itaconate can be taken up by tumor cells and its mechanism of action remain largely unclear. Here, we identified solute carrier family 13 member 3 (SLC13A3) as a key protein transporting extracellular itaconate into cells, where it elevates programmed cell death ligand 1 (PD-L1) protein levels and decreases the expression of immunostimulatory molecules, thereby promoting tumor immune evasion. Mechanistically, itaconate alkylates the cysteine 272 residue on PD-L1, antagonizing PD-L1 ubiquitination and degradation. Consequently, SLC13A3 inhibition enhances the efficacy of anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) immunotherapy and improves the overall survival rate in syngeneic mouse tumor models. Collectively, our findings identified SLC13A3 as a key transporter of itaconate and revealed its immunomodulatory role, providing combinatorial strategies to overcome immunotherapy resistance in tumors.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症免疫治疗
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Qian Lei,Yaoyu Zhang,Tongtong Yang,Lei Chen,Xinxin Pei,Yujie Zhang,Tengfei Ma,Yuzhu Xie,Yi Wang,Hongxia Li,Cheng Cao,Buchang Zhang,Changzhi Xu
Listeria monocytogenes infection often leads to listeriosis in immunocompromised individuals, and screening for potential nutrients that improve immunity may be beneficial. Here, we found that pre-incubation with heptadecanoic acid (C17:0), an odd-chain saturated fatty acid, significantly inhibited L.monocytogenes replication in differentiated THP-1 and RAW264.7, as evidenced by comparison of listeriolysin expression and colony count. Mechanistically, the administration of C17:0 triggered the activation of the IFN and NF-κB signaling pathways. Furthermore, C17:0 upregulated ACOD1 expression and the generation of itaconate, an anti-bacterial metabolite in macrophages. Based on these results, our comparative analysis showed that sheep tail fat (STF), ruminant lipid rich in C17:0, had similar anti- L.monocytogenes effect. Collectively, our data highlighted the function of C17:0 in boosting the immune response, shedding light on the application of C17:0 and STF as potential candidates for strengthening anti- L.monocytogenes response.
研究领域:
免疫学
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微生物学
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营养学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）