Inflammation最新文献

Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-25 DOI: 10.1007/s10753-025-02289-2

Xiaoshan Wang, Nuli Xie, Hanyong Zhang, Wenhu Zhou, Jiandu Lei

{"title":"Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination.","authors":"Xiaoshan Wang, Nuli Xie, Hanyong Zhang, Wenhu Zhou, Jiandu Lei","doi":"10.1007/s10753-025-02289-2","DOIUrl":"https://doi.org/10.1007/s10753-025-02289-2","url":null,"abstract":"Isoorientin (ISO) is a flavonoid compound with potential antioxidant and antiatherosclerotic properties. This investigation delves into the impact of ISO on macrophage pyroptosis in atherosclerosis (AS) progression and probes its functional mechanism. ApoE-/- mice were fed a high-fat diet for AS modeling. ISO treatment significantly alleviated atherosclerotic lesions, lipid accumulation, the necrotic core area, and macrophage pyroptosis in model mice. In vitro, ISO reduced oxidized low-density lipoprotein-induced pyroptosis in mouse bone marrow-derived macrophages. The mechanism underlying these effects is linked to a reduction in lysine demethylase 4A (KDM4A) levels in macrophages. Artificial restoration of KDM4A levels reversed the protective effects of ISO and promoted atherogenesis. KDM4A was found to inhibit the transcription of S-phase kinase-associated protein 1 (SKP1), leading to impaired SKP1-Cullin1-F-box (SCF) E3 ligase-mediated ubiquitination of NLR family pyrin domain containing 3 (NLRP3). This disruption promoted NLRP3 inflammasome assembly and activation. Artificial SKP1 overexpression reduced NLRP3 levels and reversed the protective effects of ISO. In conclusion, this study demonstrated that ISO inhibits macrophage pyroptosis and atherogenesis by reducing KDM4A levels and restoring SCF complex-mediated ubiquitination of NLRP3.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Puerarin Ameliorates Sarcopenia in Aged Mice via Modulation of Inflammation and Oxidative Stress: Insights from Proteomics and Transcriptomics.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-24 DOI: 10.1007/s10753-025-02274-9

Shangjin Lin, Ying Cheng, Tao Cui, Fengjian Yang, Shengwu Yang, Yongqian Fan

{"title":"Puerarin Ameliorates Sarcopenia in Aged Mice via Modulation of Inflammation and Oxidative Stress: Insights from Proteomics and Transcriptomics.","authors":"Shangjin Lin, Ying Cheng, Tao Cui, Fengjian Yang, Shengwu Yang, Yongqian Fan","doi":"10.1007/s10753-025-02274-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02274-9","url":null,"abstract":"Sarcopenia, a chronic degenerative condition associated with aging, is characterized by a significant decline in muscle mass and strength. Puerarin, a major active isoflavone extracted from Pueraria lobata, exhibits potent anti-inflammatory and antioxidant properties. However, its therapeutic effects on sarcopenia remain unclear. Thus, the purpose of this study was to evaluate the therapeutic effects and underlying molecular mechanisms of puerarin in ameliorating sarcopenia in naturally aged mice. Twenty-month-old male C57BL/6 J aged mice were randomly divided into two groups based on body weight: the puerarin group (puerarin dissolved in double-distilled water, 150 mg/kg/day) and the control group (equal volume of double-distilled water). After an 8-week intervention, changes in muscle mass and function between the two groups were compared. Techniques such as HE staining, immunofluorescence staining, ELISA, transmission electron microscopy, Western blot, and qRT-PCR were employed to evaluate the positive effects of puerarin on sarcopenia in naturally aged mice. Furthermore, serum proteomics and muscle transcriptomics were used to analyze the molecular mechanisms underlying the anti-muscle atrophy effects of puerarin. The results demonstrated that puerarin significantly improved body composition, enhanced muscle mass and function, and exerted its effects by modulating inflammatory cytokines, reducing oxidative stress, and inhibiting the expression of apoptosis proteins in skeletal muscle. Additionally, integrated proteomics and transcriptomics analyses suggested that the anti-muscle atrophy mechanisms of puerarin might be related to the TNF-α/NF-κB signaling pathway. These findings highlight puerarin's potential as a therapeutic agent for sarcopenia, providing a foundation for further research and clinical application.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

E3 Ubiquitin Ligase FBXO32 Promotes LPS-Induced Cardiac Injury by Regulating ANXA1/PI3K/AKT Signaling.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-24 DOI: 10.1007/s10753-025-02273-w

De Chen, Xuan Liang, Lei Zhang, Jingjing Zhang, Lina Gao, Dong Yan, Kun Zuo, Hong Guo, Song Du, Jian Liu

{"title":"E3 Ubiquitin Ligase FBXO32 Promotes LPS-Induced Cardiac Injury by Regulating ANXA1/PI3K/AKT Signaling.","authors":"De Chen, Xuan Liang, Lei Zhang, Jingjing Zhang, Lina Gao, Dong Yan, Kun Zuo, Hong Guo, Song Du, Jian Liu","doi":"10.1007/s10753-025-02273-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02273-w","url":null,"abstract":"Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis. Therefore, understanding SIC pathogenesis and developing new therapeutic targets are of great significance. This study investigated the role of F-box-only protein 32 (FBXO32) in SIC pathogenesis. LPS-induced cardiac injury models were established in rats and H9c2 cells using lipopolysaccharide. The effects of FBXO32 on myocardial apoptosis and mitochondrial structure and function were determined using electron microscopy, reactive oxygen species detection, and JC-1 staining. The molecular mechanism was elucidated using western blotting and co-immunoprecipitation. The results showed elevated FBXO32 expression in both in vivo and in vitro LPS-induced cardiac injury models. Fbxo32 knockdown alleviated apoptosis and mitochondrial and cardiac dysfunction. Mechanistic analysis revealed that FBXO32 promoted ubiquitination and degradation of annexin A1 (ANXA1), inhibiting the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) pathways. Rescue experiments demonstrated that Anxa1 knockdown reversed the effects of Fbxo32 knockdown. This study suggests that FBXO32 exacerbates LPS-induced cardiac injury progression by mediating ANXA1 ubiquitination and inhibiting the PI3K/AKT signaling pathway.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SUCNR1 Deficiency Alleviates Liver Ischemia-Reperfusion Injury by Regulating Kupffer Cell Activation and Polarization Through the ERK/NF-κB Pathway in Mice.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-19 DOI: 10.1007/s10753-025-02290-9

Huan Yang, An Wei, Xinting Zhou, Zhiwei Chen, Yiheng Wang

{"title":"SUCNR1 Deficiency Alleviates Liver Ischemia-Reperfusion Injury by Regulating Kupffer Cell Activation and Polarization Through the ERK/NF-κB Pathway in Mice.","authors":"Huan Yang, An Wei, Xinting Zhou, Zhiwei Chen, Yiheng Wang","doi":"10.1007/s10753-025-02290-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02290-9","url":null,"abstract":"Succinate regulates inflammation through its receptor, succinate receptor 1 (SUCNR1). However, the effects of this interaction on Kupffer cell (KC)-driven inflammation during liver ischemia-reperfusion injury (IRI) remain unclear. Herein, we investigated the succinate/SUCNR1 axis in the progression of liver IRI. In this study, succinate levels and SUCNR1 expression were analyzed in mice underwent segmental liver IRI. Sucnr1 deficiency (Sucnr1-/-) and Wild-type mice were treated with or without clodronate before liver IRI modeling, and a co-culture system was established to assess the impact of Sucnr1 deficiency in KCs on hepatocyte viability and apoptosis. KC activation status and polarization were determined, in vivo and in vitro. Furthermore, the downstream pathways in regulating KC polarization were investigated. We observed a significant increase in succinate levels in the serum and liver, and SUCNR1 expression in KCs after IRI. Sucnr1 deletion alleviated liver IRI and hepatocyte apoptosis either in vivo or in vitro. However, the aforementioned hepatoprotective effects were abolished by the depletion of KCs with clodronate. Sucnr1 deletion inhibited KC activation and M1 polarization, and dampened proinflammatory cytokine release after liver IRI. In addition, Sucnr1 knockout reversed the increasing phosphorylation of ERK and NF-κB p65 in KCs following liver IRI. The phosphorylation of ERK/NF-κB p65 and M1 polarization in KCs were also inhibited by the SUCNR1 antagonist Compound 4C or ERK inhibitor SCH772984. Together, these findings suggest that SUCNR1 deficiency protects against liver IRI by modulating KC activation and polarization probably through the ERK/NF-κB pathway.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long Non-coding RNA MIR22HG Alleviates Ischemic Acute Kidney Injury by Targeting the miR-134-5p/NFAT5 axis. 长非编码 RNA MIR22HG 通过靶向 miR-134-5p/NFAT5 轴缓解缺血性急性肾损伤

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-17 DOI: 10.1007/s10753-025-02286-5

Jingdong Li, Zhe Dong, Liting Tang, Lu Liu, Cuijing Su, Shan Yu

{"title":"Long Non-coding RNA MIR22HG Alleviates Ischemic Acute Kidney Injury by Targeting the miR-134-5p/NFAT5 axis.","authors":"Jingdong Li, Zhe Dong, Liting Tang, Lu Liu, Cuijing Su, Shan Yu","doi":"10.1007/s10753-025-02286-5","DOIUrl":"https://doi.org/10.1007/s10753-025-02286-5","url":null,"abstract":"Acute kidney injury (AKI), often triggered by ischemia-reperfusion (I/R) injury, is a critical condition characterized by rapid loss of renal function, leading to high morbidity and mortality. Despite extensive research, therapeutic options for ischemic AKI remain limited, and understanding the molecular mechanisms involved is crucial for developing targeted therapies. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various diseases, including cancer and renal injury. This study investigates the role of the lncRNA MIR22HG in mitigating renal injury during ischemic AKI. Using in vivo and in vitro models of I/R-induced AKI in mice and hypoxia/reoxygenation (H/R)-treated renal cells, we demonstrated that MIR22HG expression is significantly downregulated in ischemic AKI conditions. Functional assays showed that overexpression of MIR22HG in these models led to reduced renal cell apoptosis, inflammation, and improved renal function. Mechanistically, MIR22HG exerted its protective effects by negatively regulating miR-134-5p, which in turn alleviated renal injury by upregulating NFAT5, a transcription factor known to mitigate cellular stress. Furthermore, dual-luciferase and RNA pull-down assays confirmed direct interactions between MIR22HG and miR-134-5p, as well as miR-134-5p and NFAT5. Additionally, loss-and-gain-of-function assays demonstrated that overexpression of MIR22HG led to the upregulation of NFAT5, which mitigated renal apoptosis, and inflammation and improved renal function. Collectively, the results of our study highlight the therapeutic potential of targeting the MIR22HG/miR-134-5p/NFAT5 axis in the treatment of ischemic AKI, providing new insights into the molecular regulation of renal cell survival and repair during injury.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglial Annexin A3 Downregulation Alleviates Ischemic Injury by Inhibiting NF-κB/NLRP3-mediated Inflammation.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-15 DOI: 10.1007/s10753-025-02287-4

Zengli Zhang, Mengxue Zhang, Dan Li, Ruichen Shu, Qian Pan, Wangyuan Zou, Kaiyuan Wang, Yiqing Yin

{"title":"Microglial Annexin A3 Downregulation Alleviates Ischemic Injury by Inhibiting NF-κB/NLRP3-mediated Inflammation.","authors":"Zengli Zhang, Mengxue Zhang, Dan Li, Ruichen Shu, Qian Pan, Wangyuan Zou, Kaiyuan Wang, Yiqing Yin","doi":"10.1007/s10753-025-02287-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02287-4","url":null,"abstract":"Microglial inflammation is a hallmark of ischemic stroke. Annexin A3 (ANXA3) is expressed in microglia and plays a detrimental role in stroke. However, the role of ANXA3 in microglial inflammation after ischemic stroke is unclear. In this study, an ischemic stroke model was established in mice via middle cerebral artery occlusion (MCAO). The adeno-associated virus shANXA3 (AAV-shANXA3) was injected into ipsilateral cortex ischemic lesion, and the infarction volume, neurological score, and neuronal injury were examined. Moreover, primary microglia were transfected with a lentivirus (LV-shANXA3) and subjected to oxygen-glucose deprivation (OGD). Neuron viability and lactose dehydrogenase (LDH) levels of neurons cocultured with microglia were analyzed. Additionally, microglial activation and ANXA3, p-NF-κB, NLRP3 and downstream proteins of NLRP3 inflammasome (cleaved caspase-1, N-GSDMD and IL-1β) expression levels were measured. We found that microglial ANXA3 expression was increased after ischemic injury and that ANXA3 knockdown reduced the infarction volume, mitigated neurological deficits, and alleviated neuronal injuries. Additionally, ANXA3 knockdown ameliorated microglial activation and reduced the levels of p-NF-κB and inhibited NLRP3 inflammasome signaling. Furthermore, ANXA3 upregulation resulted in decreased IκBα levels, whereas ANXA3 downregulation resulted in increased IκBα levels. Notably, IκBα knockdown blocked the neuroprotective effects of AAV-shANXA3 against ischemic injury. In conclusion, microglial ANXA3 downregulation alleviates ischemic stroke by inhibiting NF-κB/NLRP3-mediated microglial inflammation, which indicates that ANXA3 may be a potential therapeutic target for ischemic stroke.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toll Like Receptors Promote High Glucose-Induced Vascular Endothelial Cell Dysfunction by Regulating Neutrophil Extracellular Traps Formation.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-15 DOI: 10.1007/s10753-025-02283-8

Shirou Wu, Yahui Chen, Xiuming Jin, Jiayun Yu, Xueping Chen, Ting Wan

{"title":"Toll Like Receptors Promote High Glucose-Induced Vascular Endothelial Cell Dysfunction by Regulating Neutrophil Extracellular Traps Formation.","authors":"Shirou Wu, Yahui Chen, Xiuming Jin, Jiayun Yu, Xueping Chen, Ting Wan","doi":"10.1007/s10753-025-02283-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02283-8","url":null,"abstract":"Diabetic retinopathy (DR) is a major cause of blindness globally. Neutrophils and neutrophil extracellular traps (NETs) are believed to play a role in the development of DR. However, the specific contribution of NETs to hyperglycemia-induced vascular endothelial cell dysfunction remains unclear. In this study, we cocultured high glucose-activated neutrophils (HGNs) with human umbilical vein endothelial cells (HUVECs) to investigate the role of NETs in high glucose-induced HUVEC dysfunction. Our findings indicate that high glucose levels promote NETs formation, which can be inhibited by a toll-like receptor (TLR) 2 antagonist and a TLR4 antagonist. It was observed that reactive oxygen species production plays a role in TLR2- but not TLR4-mediated NETs formation. Additionally, HGNs were found to promote HUVEC proliferation through phagocytosis rather than NETs. We also discovered that NETs contribute to high glucose-induced HUVEC dysfunction by enhancing neutrophil-HUVEC adhesion, inhibiting HUVEC migration, and compromising the barrier function of the cells by reducing zonula occludens-1 expression. This dysfunction could be partially mitigated by TLR2 and TLR4 antagonists. In conclusion, high glucose stimulates NETs formation, leading to vascular endothelial cell damage, and TLRs may facilitate high glucose-induced endothelial dysfunction by modulating NETs formation.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TXM-CB13 Improves the Intestinal Mucosal Barrier and Alleviates Colitis by Inhibiting the ROS/TXNIP/TRX/NLRP3 and TLR4/MyD88/NF-κB/NLRP3 Pathways.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-14 DOI: 10.1007/s10753-025-02282-9

Ruijie Cao, Jinhui Zhou, Jiale Liu, Yaxuan Wang, Yandong Dai, Yun Jiang, Akira Yamauchi, Daphne Atlas, Tiancheng Jin, Jiedong Zhou, Cuixue Wang, Qihuan Tan, Yifei Chen, Junji Yodoi, Hai Tian

{"title":"TXM-CB13 Improves the Intestinal Mucosal Barrier and Alleviates Colitis by Inhibiting the ROS/TXNIP/TRX/NLRP3 and TLR4/MyD88/NF-κB/NLRP3 Pathways.","authors":"Ruijie Cao, Jinhui Zhou, Jiale Liu, Yaxuan Wang, Yandong Dai, Yun Jiang, Akira Yamauchi, Daphne Atlas, Tiancheng Jin, Jiedong Zhou, Cuixue Wang, Qihuan Tan, Yifei Chen, Junji Yodoi, Hai Tian","doi":"10.1007/s10753-025-02282-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02282-9","url":null,"abstract":"The activation of inflammasomes (NLRP3 and NLRP1) is central to the pathogenesis of inflammatory bowel disease (IBD). Here we examined the protective effects of a thioredoxin-mimetic peptide CB13 (TXM-CB13), known for its antioxidative stress and anti-inflammatory properties. We examined the effects of TXM-CB13 on dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation in RAW264.7 macrophages. TXM-CB13 appeared to alleviate symptoms of DSS-induced colitis and to significantly suppress the protein and mRNA levels of NLRP3, Mlck, and IL-1β in colonic tissues. Additionally, TXM-CB13 treatment increased the levels of the intestinal barrier proteins Occludin, ZO-1, and NLRP1, as shown through immunohistochemistry and Western blot analysis. In vitro, TXM-CB13 inhibited LPS-induced TLR4 signaling, reducing MyD88 levels and consequently attenuating the activation of the NF-κB pathways, including p-IκB-α/IκB-α and p-NF-κB-p65/NF-κB-p65. This inhibition further reduced the activation of the NLRP3 inflammasome components, NLRP3, ASC, Caspase-1, GSDMD, and IL-1β. In addition, TXM-CB13 prevented the ROS-mediated dissociation of TXNIP from TRX, inhibiting NLRP3 activation. These findings suggest that TXM-CB13 is a potential therapeutic candidate for IBD through its modulation of the TLR4/MyD88/NF-κB/NLRP3 and ROS/TXNIP/TRX/NLRP3 pathways.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Canagliflozin Attenuates Podocyte Inflammatory Injury through Suppressing the TXNIP/NLRP3 Signaling Pathway in Diabetic Kidney Disease Mice.

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-11 DOI: 10.1007/s10753-025-02258-9

Siyu Li, Jie Wang, Ying Chen, Yanlu Cheng, Yanan Wang, Nuowen Xu, Hao Wang, Li Wang, Yangfeng Chi, Xiaoxue Ye, Yanting Shi, Ji Fang, Xingmei Yao, Jiebo Huang, Qing Xia, Tianli Bai, Bingbing Zhu

{"title":"Canagliflozin Attenuates Podocyte Inflammatory Injury through Suppressing the TXNIP/NLRP3 Signaling Pathway in Diabetic Kidney Disease Mice.","authors":"Siyu Li, Jie Wang, Ying Chen, Yanlu Cheng, Yanan Wang, Nuowen Xu, Hao Wang, Li Wang, Yangfeng Chi, Xiaoxue Ye, Yanting Shi, Ji Fang, Xingmei Yao, Jiebo Huang, Qing Xia, Tianli Bai, Bingbing Zhu","doi":"10.1007/s10753-025-02258-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02258-9","url":null,"abstract":"Diabetic kidney disease (DKD), a leading cause of end-stage renal disease (ESRD), poses a serious threat to global health. Aseptic inflammation and pyroptosis of podocytes are crucial factors contributing to the pathogenesis and progression of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a novel class of antidiabetic agents widely used in clinical settings, may exert a protective effect on podocyte injury, although the underlying mechanisms remain poorly understood. This study uses the streptozotocin (STZ) -induced DKD mouse model to further explore the mechanism by which SGLT2i protect podocytes. The results demonstrated that Canagliflozin (CANA) treatment significantly improved serum creatinine levels, 24-h urinary albumin excretion, and urinary albumin-to-creatinine ratio (UACR) in DKD mice. Additionally, CANA treatment attenuated glomerular and podocyte injury, reducing overall pathological damage. Mechanistically, CANA reduced the expression of key inflammatory markers in the renal cortex of DKD mice, including TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, and GSDMD. These findings suggest that CANA may be an effective therapeutic agent for DKD by inhibiting the TXNIP-NLRP3 inflammasome pathway and preventing podocyte pyroptosis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

"The Ameliorative Effect of Interleukin-17A Neutralization on Doxorubicin-Induced Cardiotoxicity by Modulating the NF-κB/NLRP3/Caspase-1/IL-1β Signaling Pathway in Rats".

IF 4.5 2区医学

Inflammation Pub Date : 2025-03-11 DOI: 10.1007/s10753-024-02187-z

Mostafa D Hassen, Nahla O Mousa, Sara M Radwan, Refaat M Gabre

{"title":"\"The Ameliorative Effect of Interleukin-17A Neutralization on Doxorubicin-Induced Cardiotoxicity by Modulating the NF-κB/NLRP3/Caspase-1/IL-1β Signaling Pathway in Rats\".","authors":"Mostafa D Hassen, Nahla O Mousa, Sara M Radwan, Refaat M Gabre","doi":"10.1007/s10753-024-02187-z","DOIUrl":"https://doi.org/10.1007/s10753-024-02187-z","url":null,"abstract":"Doxorubicin (DOX) is used as a chemotherapeutic drug for treating cancer. Nevertheless, it causes damage to the heart by activating inflammatory pathways, resulting in cardiotoxicity. Imbalance in cytokine production is a crucial component that might trigger the initiation of inflammatory processes. Inflammatory cytokines could be targeted therapies against cardiovascular diseases (CVDs). Interleukin-17A (IL-17A) is a cytokine that promotes inflammation and stimulates harmful immunological reactions. The objective of the study was to determine the efficacy of secukinumab (SEC), a completely human monoclonal IgG1/κ antibody that targets IL-17A, in ameliorating DOX-induced cardiotoxicity (DIC). We administered 2.5 mg/kg of DOX intraperitoneally to male Wistar rats three times a week for 2 weeks and simultaneously administered 0.9 mg/kg of SEC along with 2.5 mg/kg of DOX injection three times a week for a duration of two weeks. The findings indicated that DOX induced damage to the heart tissue, resulting in a significant rise in indicators of cardiotoxicity (P < 0.001), as well as oxidative stress and inflammation. DIC may have arisen from DOX's activation of the Pyrin domain containing 3 (NLRP3) inflammasome and the nuclear factor kappa beta (NF-κB) pathway. The co-administration of SEC successfully reversed all DOX-induced abnormalities by restoring cardiac functions to their baseline levels, decreasing levels of inflammatory mediators such as IL-17A and interleukin-1β (IL-1β), and improving oxidative stress by reducing levels of malondialdehyde (MDA) and increasing levels of reduced glutathione (GSH). Furthermore, it mitigated the heightened activation of the NF-κB/NLRP3 pathway caused by DOX. This study shows that IL-17A neutralization can prevent DIC by regulating the NF-κB/NLRP3/Caspase-1/IL-1β pathway to be used as potential therapeutic target for CVDs.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0