PLoS One
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2025
·Vol. 20
·期 4
·e0319605
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IF 2.6
Hong-Fei He,Shuang Hou,Xiao-Ya Ma,Song-song Huang,Bo Yang,Jun-Kang Wang,Yuan Xu,Lei Tan,Hai-Yang Li
As one of the major causes of acute kidney injury, renal ischemia-reperfusion is a common health problem in a series of clinical situations, including renal transplantation. Although the mechanisms of renal IRI have been widely investigated, effective strategies are still in lacking for its prevention and treatment. In previous study, we found that the down-regulation of taurine upregulated gene 1, a long non-coding RNA (lncRNA TUG1), markedly alleviated renal IRI through mitigating the cell inflammation and apoptosis. At meanwhile, YTHDF2, an RNA methylation reading protein, was identified as a vital player in IRI of distinct organs, however, not reported in kidney. We then conducted the current study on the function of YTHDF2 in renal IRI and its regulatory role to TUG1. Based on renal IRI models in vitro and in vivo, dramatical down-regulation of YTHDF2 was presented. Subsequently, exogenous perturbation of YTHDF2 was conducted and its protective effects on cell apoptosis were demonstrated in acute IRI exogenous. Furthermore, with the same model, it was indicated that YTHDF2 protein negative regulated TUG1 RNA via direction interaction. Since then, YTHDF2 was proved as a potential protector of renal IRI through restraining of TUG1. In further speculation, induction of YTHDF2 in IRI will possibly become a possible strategy to combat the pathological process post renal transplantation or other clinical conditions.
研究领域:
分子生物学
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肾脏病学
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医学
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产品关联
DOI
PubMed
高影响因子
Human Cell
·
2025
·Vol. 38
·期 2
·1-16
·
IF 3.1
Zhang Lexi,Ye Jianfeng,Qiu Cheng
Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Twist-related protein 2 (Twist2) is a basic helix/loop/helix transcription factor. However, the underlying effects of Twist2 in IRI remain to be elucidated. Herein, we found that the expression of Twist2 was significantly upregulated in renal tissues of mice induced by ischemia/reperfusion (I/R) and in human renal tubular epithelial cell HK-2 exposed to hypoxia–reoxygenation. We silenced Twist2 with RNAi technology. Twist2 knockdown alleviated renal pathological damage in mice. Twist2 depletion ameliorated IRI-induced mitochondrial dysfunction, such as increasing ATP content and mitochondrial DNA copy number and restoring mitochondrial membrane potential in the kidneys of mice , and similar results were observed in in vitro experiments. Twist2 interference increased the expression of LC3B and decreased the expression of p62 and mitochondrial membrane proteins TIMM23 and TOMM20 both in vivo and in vitro. Electron microscope and the co-localization of LC3B and mitotracker DsRed suggested the induction of autophagy and mitophagy after Twist2 knockdown in kidneys or cells. Mechanism studies revealed that Twist2 exerted a direct inhibitory effect on BCL2 interacting protein 3 (Bnip3) transcriptional activity by targeting the Bnip3 promoter. In hypoxia/reoxygenation-induced renal tubular epithelial cells, the interference of Bnip3 reversed the effect of Twist2 depletion on mitochondrial function and mitophagy. In conclusion, our findings suggest that the depletion of Twist2 exerts renoprotective effect in I/R-induced AKI. Twist2 regulates mitochondrial function and mitophagy in part by targeting and downregulating Bnip3. Our study provides new insights into the pathological mechanisms of I/R-induced AKI.
研究领域:
肾病学
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2025
·
IF 3.9
Binlin Chen,Yueqi Deng,Qingjing Niu,Kongying Zhu,Lixia Ren,Xiaoyan Yuan
Ice formation poses a significant challenge across various fields, from industrial processes to biological preservation. Developing antifreeze agents and recognizing the antifreeze mechanism have gained considerable attention. Herein, a series of poly(l-methionine) derivatives, poly(S-carboxymethyl-l-methionine sulfonium) (PMetA), poly(S-methyl-l-methionine sulfonium chloride) (PMetM), and poly(S-carbamidomethyl-l-methionine sulfonium chloride) (PMetAM), with carboxyl, methyl, and acetamide groups, respectively, are synthesized and investigated for antifreeze. The relationship between the polymer structure and the ice recrystallization inhibition (IRI) activity is examined, suggesting that zwitterionic PMetA shows the highest IRI activity, about 27.0 ± 3.9% at 10 mg mL–1 relative to that of water. Results of low-field nuclear magnetic resonance and differential scanning calorimetry indicate that the IRI activity is associated with the activation energy for hydrogen bond breakage. PMetA exhibits acceptable cytocompatibility at 10.0 mg mL–1 and a good cryoprotective efficiency. This finding provides a valuable insight into the antifreeze mechanism, contributing to the development of potent cryoprotectants.
研究领域:
材料科学
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生物物理学
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低温生物学
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聚合物化学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Zhizhao Deng,Weiqi Zeng,Yingxin Gao,Zhenyu Yang,Xinling Luo,Xianlong Li,Guoliang Sun,Erfeng Xiong,Fei Huang,Gangjian Luo,Ziqing Hei,Dongdong Yuan
Ischemia-reperfusion injury (IRI) is the leading cause of hepatic graft dysfunction, resulting from hepatocyte damage. Nevertheless, given the few specialized therapeutics available in hepatic IRI, additional mechanistic insights into hepatocyte damage are required. Here, the protein solute carrier family 39 member 14 (SLC39A14) is identified as a pro-ferroptosis target in hepatocytes of human liver allografts through single-cell RNA sequencing analysis. SLC39A14 knockdown significantly mitigated hepatic IRI by preventing hepatocyte ferroptosis in vivo and in vitro. Mechanistically, the inhibition of SLC39A14 suppressed non-transferrin-bound iron (NTBI) uptake by hepatocytes, thereby reducing iron overload and cell ferroptosis. Moreover, human bone marrow-derived mesenchymal stem cells (hBMSCs) are found to exhibit a notable therapeutic effect on hepatic IRI by downregulating SLC39A14 expression. Exosomes derived from hBMSCs delivered abundant miR-16-5p into hepatocytes, which post-transcriptionally suppressed the expression of SLC39A14 and reduced cell ferroptosis induced by hepatic IRI. In conclusion, SLC39A14 triggers hepatic IRI by mediating NTBI uptake into hepatocytes and inducing hepatocyte ferroptosis. Moreover, hBMSC-based therapy is promising to reverse this progression of hepatic IRI.
研究领域:
干细胞治疗
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分子生物学
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肝病学
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器官移植
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DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Liu Bin,Li Faping,Wang Yuxiong,Gao Xin,Li Yunkuo,Wang Yishu,Zhou Honglan
Background: Kidney injuries often carry a grim prognosis, marked by fibrosis development, renal function loss, and macrophage involvement. Despite extensive research on macrophage polarization and its effects on other cells, like fibroblasts, limited attention has been paid to the influence of non-immune cells on macrophages. This study aims to address this gap by shedding light on the intricate dynamics and diversity of macrophages during renal injury and repair.Methods: During the initial research phase, the complexity of intercellular communication in the context of kidney injury was revealed using a publicly available single-cell RNA sequencing library of the unilateral ureteral obstruction (UUO) model. Subsequently, we confirmed our findings using an independent dataset from a renal ischemia-reperfusion injury (IRI) model. We treated two different types of endothelial cells with TGF-β and co-cultured their supernatants with macrophages, establishing an endothelial cell and macrophage co-culture system. We also established a UUO and an IRI mouse model. Western blot analysis, flow cytometry, immunohistochemistry and immunofluorescence staining were used to validate our results at multiple levels.Results: Our analysis revealed significant changes in the heterogeneity of macrophage subsets during both injury processes. Amyloid β precursor protein (APP)-CD74 axis mediated endothelial-macrophage intercellular communication plays a dominant role. In the in vitro co-culture system, TGF-β triggers endothelial APP expression, which subsequently enhances CD74 expression in macrophages. Flow cytometry corroborated these findings. Additionally, APP and CD74 expression were significantly increased in the UUO and IRI mouse models. Immunofluorescence techniques demonstrated the co-localization of F4/80 and CD74 in vivo.Conclusion: Our study unravels a compelling molecular mechanism, elucidating how endothelium-mediated regulation shapes macrophage function during renal repair. The identified APP-CD74 signaling axis emerges as a promising target for optimizing renal recovery post-injury and preventing the progression of chronic kidney disease.
研究领域:
肾病学
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免疫学
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分子生物学
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细胞生物学
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病理生理学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Dong Mo,Wei Cui,Linxin Chen,Juanjuan Meng,Yuting Sun,Kaiyong Cai,Jixi Zhang,Jianrong Zhang,Kui Wang,Xiaohe Luo
Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.
研究领域:
药理学
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纳米技术
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肝病学
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免疫学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
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