Journal of the Renin-Angiotensin-Aldosterone System最新文献

HIF-responsive lncRNAs define an immunosuppressive phenotype and predict anti-angiogenic response in clear cell renal cell carcinoma hif应答lncrna定义了透明细胞肾细胞癌的免疫抑制表型并预测了抗血管生成反应

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2026-01-01 DOI: 10.1177/14703203251401461

Yi Huang, W. Zhang, Wenhao Xu, Leilei Du, X. Zhang, Wenfeng Wang, Guohai Shi, J Wang

{"title":"HIF-responsive lncRNAs define an immunosuppressive phenotype and predict anti-angiogenic response in clear cell renal cell carcinoma","authors":"Yi Huang, W. Zhang, Wenhao Xu, Leilei Du, X. Zhang, Wenfeng Wang, Guohai Shi, J Wang","doi":"10.1177/14703203251401461","DOIUrl":"https://doi.org/10.1177/14703203251401461","url":null,"abstract":"Hypothesis/Introduction Hypoxia defines clear cell renal cell carcinoma (ccRCC), but its transcriptional and therapeutic consequences are unclear. We hypothesized that a specific hypoxia-induced long noncoding RNA (lncRNA) signature links VHL–HIF signaling to immune modulation and anti-angiogenic therapy response. Materials and Methods We integrated multi-cohort transcriptomic data to prioritize hypoxia-associated lncRNAs in ccRCC. Direct regulation of candidate lncRNAs by HIF-1α was validated using ChIP-qPCR, and functional assays in RCC cell lines involving HIF-1α silencing, ectopic VHL expression, and HIF-1α overexpression. The tumor microenvironment and therapeutic vulnerabilities were analyzed using bioinformatic tools. Results We identified a five-lncRNAs signature, with AP004372.1 and AC046143.3 confirmed as direct HIF-1α transcriptional targets. This signature defined an immunosuppressive milieu with high Tregs, elevated checkpoints ( PD-1 , CTLA4 , TIGIT ), and inhibitory cytokines. These tumors also showed heightened predicted sensitivity to VEGF-targeted therapies (sunitinib, pazopanib). Conclusions Our study uncovers a hypoxia-regulated lncRNA circuit that is directly driven by HIF-1α and functionally connected to immune evasion and angiogenic dependency. This program provides a mechanistic and clinically actionable framework for stratifying ccRCC patients beyond conventional classifiers.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147906678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-07-10 DOI: 10.1177/14703203251356435

Mingxia Gu, Li Du, Changqing Mao

{"title":"Ferroptosis-related gene DUSP1 improves renal fibrosis in immunoglobulin A nephropathy through regulating p38 MAPK/Nrf2-induced ferroptosis","authors":"Mingxia Gu, Li Du, Changqing Mao","doi":"10.1177/14703203251356435","DOIUrl":"https://doi.org/10.1177/14703203251356435","url":null,"abstract":"Background Immunoglobulin A nephropathy (IgAN) is a common primary glomerular disease linked to ferroptosis. We aimed to identify key ferroptosis-related genes in IgAN and clarify their mechanism. Methods Based on the data from GEO, FerrDb, Genecards, and previous publications, differential expression analysis, Machine learning (LASSO and SVM-RFE), and Weighted correlation network Analysis were exploited to screen the ferroptosis-related genes in IgAN. Furthermore, immune infiltration analysis, GSEA, and receiver operator characteristic curve were performed to identify the key genes and evaluate their diagnostic ability. A TGF-β1-induced HK-2 cell model of fibrosis with oe-DUSP1 transfection and treatment with the p38 MAPK activator U-46619 was used to validate the findings. Results We identified 23 ferroptosis-related differential expressed genes in IgAN, enriched in ECM-receptor interaction, focal adhesion, and allograft rejection. Four genes (CDO1, NR4A1, JUN, DUSP1) exhibited promising diagnostic value in IgAN (AUC > 0.90). NR4A1 and DUSP1 were down-regulated in IgAN and correlated with immune cell infiltration like Eosinophil, immature B cell, and activated B cell. DUSP1 overexpression inactivated p38 MAPK, increased Nrf2 and ferroptosis markers (GPX4 and SLC7A11), decreased Fe 2+ and fibrosis. U-46619 addition had no effects on DUSP1, but reversed above alterations. Conclusions NR4A1 and DUSP1 are key diagnostic markers in IgAN, with DUSP1 modulating fibrosis via p38 MAPK/Nrf2-mediated ferroptosis.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147917859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Dose-dependent effects of the ACE inhibitor, ramipril, on kidney function and structure in the Alport COL4A3 ^−/− mouse ACE抑制剂雷米普利对Alport COL4A3 - / -小鼠肾脏功能和结构的剂量依赖性影响

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-07-01 DOI: 10.1177/14703203251386305

Yanling Zhang, Hai Wang, Linda Nghiem, Richard E. Gilbert

{"title":"Dose-dependent effects of the ACE inhibitor, ramipril, on kidney function and structure in the Alport COL4A3 −/− mouse","authors":"Yanling Zhang, Hai Wang, Linda Nghiem, Richard E. Gilbert","doi":"10.1177/14703203251386305","DOIUrl":"https://doi.org/10.1177/14703203251386305","url":null,"abstract":"Introduction ACE inhibitor treatment of Alport syndrome, undertaken when individuals are still presymptomatic/oligosymptomatic delays dialysis but substantial residual risk remains so that additional treatments are desperately needed. In contrast to humans, standard-dose ACE inhibition with ramipril 10 mg/kg/day in Alport mice almost completely prevents GFR loss, precluding the ability to test new add-on therapies. Accordingly, we sought to find a dose that mirrored the ∼50% improvement in GFR seen in humans. Material and methods Escalating doses of ramipril at 0.1, 1, 3 and 10 mg/kg/day, were administered to COL4A3 −/− mice. Results After four weeks, ramipril induced a logarithmic, dose-dependent decline in cystatin C, the primary GFR-based outcome, with efficacy apparent at 0.1 mg/kg/day and a 50% improvement at 1–3 mg/kg/day. Proteinuria, the study's secondary outcome, showed a similar dose-response. In contrast, structural improvements such as podocyte density, glomerulosclerosis and tubulointerstitial fibrosis were not evident below 3 mg/kg/day. Conclusion By exploring the dose-response relationship of RAS blockade in an Alport model, the present study shows that ramipril 1 mg/kg/day may be sufficient for examining additive effects of other agents on kidney function while 3 mg/kg/day is required in order to assess the effects of add-on therapy on kidney structure as well.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147901621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

PXN ⁺ monocytes accelerate diabetic retinopathy progression and inflammaging via SELPLG-SELL axis-mediated immune chemotaxis and RAS modulation PXN +单核细胞通过SELPLG-SELL轴介导的免疫趋化和RAS调节加速糖尿病视网膜病变的进展和炎症

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-07-01 DOI: 10.1177/14703203251386803

Na Liang, Jing Li, Wenting Wang, Huifang Xu, Shaomin Peng

{"title":"PXN + monocytes accelerate diabetic retinopathy progression and inflammaging via SELPLG-SELL axis-mediated immune chemotaxis and RAS modulation","authors":"Na Liang, Jing Li, Wenting Wang, Huifang Xu, Shaomin Peng","doi":"10.1177/14703203251386803","DOIUrl":"https://doi.org/10.1177/14703203251386803","url":null,"abstract":"Background Diabetic retinopathy (DR), a leading cause of vision loss, arises from chronic inflammation, vascular injury, and immune dysregulation. Aging-related mechanisms, including inflammaging, further exacerbate immune activation. The renin–angiotensin-aldosterone system (RAS) has been implicated in vascular dysfunction and chronic inflammation in DR. Paxillin (PXN), a cytoskeletal adaptor regulating immune cell migration, has not been fully explored in the context of DR and aging-related immune responses. Objective To determine how PXN + monocytes contribute to DR progression, with a focus on SELPLG-SELL-mediated chemotaxis, PXN-RAS interactions, and age-related inflammatory remodeling. Methods Mendelian randomization (MR) and single-cell transcriptomics identified PXN as a putative driver of DR. Functional assays were performed in RAW264.7 macrophages with PXN overexpression or knockdown under high-glucose conditions, with or without Losartan treatment. qPCR, CCK-8, ELISA, flow cytometry, and immunoblotting were used to assess inflammatory and oxidative pathways. Results MR revealed a causal association between PXN and DR risk, highlighting the SELPLG-SELL axis as a major chemotaxis pathway. Single-cell RNA-seq showed PXN + monocytes amplify T/NK cell crosstalk and immune infiltration. PXN overexpression promoted M1 polarization, upregulated SELL/SELPLG, increased IL-6, IL-17, and IL-23 secretion, and enhanced ACE-driven oxidative stress, attenuating Losartan's anti-inflammatory effects. These findings link PXN + monocytes to inflammaging-like immune remodeling in DR. Conclusions PXN amplifies pro-inflammatory chemotaxis and immune aging in DR, undermining RAS inhibition. Targeting PXN may mitigate inflammaging-driven retinal inflammation and improve therapeutic responses in diabetic retinopathy.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147892828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

SerpinB1 promotes cardiomyocyte proliferation and heart regeneration via inhibiting ERBB2 degradation SerpinB1通过抑制ERBB2降解促进心肌细胞增殖和心脏再生

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-07-01 DOI: 10.1177/14703203251403992

Meiling Li, Shuang Qu, Xia Xu, Dachun Yang, Chengming Fan, Yongjian Yang, Cong Lan

{"title":"SerpinB1 promotes cardiomyocyte proliferation and heart regeneration via inhibiting ERBB2 degradation","authors":"Meiling Li, Shuang Qu, Xia Xu, Dachun Yang, Chengming Fan, Yongjian Yang, Cong Lan","doi":"10.1177/14703203251403992","DOIUrl":"https://doi.org/10.1177/14703203251403992","url":null,"abstract":"Adult hearts are hard to recover after injury due to postnatal loss of regenerative capacity. Induction of cell cycle reentry of adult cardiomyocytes by special treatment offers a promising regenerative therapy for heart injury. This study aims to investigate the role of serpin family B member 1 (SerpinB1) in the regulation of cardiomyocyte proliferation and heart regeneration. The expression of SerpinB1 in the mouse heart was decreased during postnatal growth and increased during neonatal heart regeneration induced by apical resection (AR), consistent with the alteration of regenerative capacity. Cardiac-specific overexpression of SerpinB1 reactivated cardiomyocyte proliferation and improved cardiac repair following myocardial infarction (MI) in adult mice. Mechanistically, we found erb-b2 receptor tyrosine kinase 2 (ERBB2) signaling activity was upregulated by SerpinB1 overexpression and administration of ERBB2 kinase inhibitor AG789 largely blunted cardiomyocyte pro-proliferative effect of SerpinB1. Further study revealed that SerpinB1 upregulated ERBB2 protein level via interacting with elastase to inhibit ERBB2 degradation and elastase overexpression blocked SerpinB1-induced cardiomyocyte proliferation in vitro . Taken together, these results highlight SerpinB1 as a critical regulator of cardiomyocyte proliferation. SerpinB1 targeting might be a novel potential therapeutic strategy for cardiac regeneration after heart injury.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147886479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

Tianma Gouteng decoction-derived nanoparticles ameliorate blood-brain barrier permeability after ischemic stroke via regulating lncRNA OIP5-AS1 and S1PR1/ERK/MEK signaling axis 天麻勾藤煎剂纳米颗粒通过调节lncRNA OIP5-AS1和S1PR1/ERK/MEK信号轴改善缺血性脑卒中后血脑屏障通透性

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-07-01 DOI: 10.1177/14703203251386327

Lu-an Weng, Luojun Zheng, Dengke Meng, Xin Zhang, Diwen Shou

{"title":"Tianma Gouteng decoction-derived nanoparticles ameliorate blood-brain barrier permeability after ischemic stroke via regulating lncRNA OIP5-AS1 and S1PR1/ERK/MEK signaling axis","authors":"Lu-an Weng, Luojun Zheng, Dengke Meng, Xin Zhang, Diwen Shou","doi":"10.1177/14703203251386327","DOIUrl":"https://doi.org/10.1177/14703203251386327","url":null,"abstract":"Background Increasing evidence suggests that herbal-derived exosome-like nanoparticles (ELNs) can easily cross biological barriers such as the blood-brain barrier (BBB). However, current understanding of ELNs application in ischemic stroke therapy is still in its infancy. Method We extracted nanoparticles (TGD-NPs) from Tianma Gouteng decoction (TGD) and characterized their morphology and main active compounds. Subsequently, the potential and functional mechanism of TGD-NPs in maintaining the integrity of the BBB were evaluated in middle cerebral artery occlusion (MCAO)-induced ischemic stroke model and oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated cell model. Result We successfully extracted NPs, which retains the main bioactive compounds of TGD: baicalin, emodin, gastrodin, and stachydrine. Functional studies indicated that in mouse MCAO model, TGD-NPs intervention was more effective than TGD preparations in maintaining the integrity of the BBB, reducing the infarct area, and improving the neurological function. Meanwhile, TGD-NPs treatment attenuated the decrease in cell viability caused by OGD/R, and it significantly enhanced expression of tight junction proteins (Occludin and ZO-1). Mechanistic exploration revealed that TGD-NPs markedly upregulated lncRNA OIP5-AS1 expression, and its beneficial effect was attributed to the activation of the S1PR1-ERK1/2-MEK1/2 signaling axis. Conclusion TGD-NPs are positive in maintaining BBB integrity and neurological function after ischemic stroke.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147899082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Visualization of the functional rescuing of GPCR homo/hetero-dimer by “silent” α _1B adrenoceptor FRET sensor “沉默”α 1B肾上腺素受体FRET传感器显示GPCR同源/异二聚体的功能挽救

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-07-01 DOI: 10.1177/14703203251399783

Ying Liu, Yuting Shao, Richard J. Ward, Li Ma, Hao-Xin Gui, Y. G. Meng, Xi Mu, Qian Hao, Yang Yang, Su An, Xiao‐Xi Guo, Cheng Xiang, Tian‐Rui Xu

{"title":"Visualization of the functional rescuing of GPCR homo/hetero-dimer by “silent” α 1B adrenoceptor FRET sensor","authors":"Ying Liu, Yuting Shao, Richard J. Ward, Li Ma, Hao-Xin Gui, Y. G. Meng, Xi Mu, Qian Hao, Yang Yang, Su An, Xiao‐Xi Guo, Cheng Xiang, Tian‐Rui Xu","doi":"10.1177/14703203251399783","DOIUrl":"https://doi.org/10.1177/14703203251399783","url":null,"abstract":"Previous studies have demonstrated that the co-expression of two mutant G protein-coupled receptors (GPCRs) can potentially restore their impaired functionality. In this study, we investigated the rescue of functional deficits in homo- and heterodimers of α1B-adrenergic receptors (ARs) using a combination of biophysical and biochemical approaches. Initially, we constructed an Förster resonance energy transfer (FRET) sensor for α1B-AR that lacked ligand-binding capability (referred to as “silent”), and a mutant α1B-AR incapable of downstream activation (referred to as “defective”). Our results revealed that the co-expression of the “defective” and “silent” α1B-ARs led to the activation of the “silent” sensor and restoration of functional impairments in both receptors. Similarly, we conducted experiments involving the co-expression of a “defective” CXCR4 receptor lacking downstream signaling and G-protein recruitment with the “silent” α1B-AR FRET sensor, which also resulted in the rescue of their functional deficiencies. These findings highlight that upon dimerization with the “defective receptor, the “silent” receptor undergoes agonist-like structural changes, leading to functional restoration. This study provides direct evidence for the functional complementation mechanism mediated by GPCR dimers and offers new insights into the intervention strategies targeting GPCR defect-related diseases.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147920192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Indolepropionic acid protects against renal fibrosis due to unilateral ureteral obstruction by enhancing the Nrf2 signaling pathway 吲哚丙酸通过增强Nrf2信号通路保护单侧输尿管梗阻引起的肾纤维化

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2025-06-01 DOI: 10.1177/14703203251350803

Haibin Yu, Lin Qi, Hongyu Li, Le Su, Yu Bai, Yanhui Liu, Xiaoyun Wang

{"title":"Indolepropionic acid protects against renal fibrosis due to unilateral ureteral obstruction by enhancing the Nrf2 signaling pathway","authors":"Haibin Yu, Lin Qi, Hongyu Li, Le Su, Yu Bai, Yanhui Liu, Xiaoyun Wang","doi":"10.1177/14703203251350803","DOIUrl":"https://doi.org/10.1177/14703203251350803","url":null,"abstract":"Objective This study investigates the protective effect of indolepropionic acid (IPA) on renal fibrosis caused by unilateral ureteral obstruction (UUO), with a focus on the Nrf2 signaling pathway. Methods A UUO model was established in 30 male SD rats (6 weeks old) via unilateral ureteral ligation. Rats were divided into sham, model, L-IPA, M-IPA, and H-IPA groups. Pathological changes and protein expressions in renal tissues were analyzed. In vitro, HK-2 cells were cultured and subjected to hypoxia for 24 h. Cells were divided into control, model, model + IPA, and model + IPA + ML385 (Nrf2 inhibitor) groups. Fibrosis and Nrf2-related protein expressions were assessed. Results In vivo, the model group exhibited severe renal damage, accompanied by increased oxidative stress and inflammatory response. The expression of α-SMA, FN, Snail1, Smad3, TGF-β1, Keap1, and HIF-1α was elevated, while Nrf2 and HO-1 levels were decreased, all of which were reversed by IPA treatment. In vitro, IPA reversed the changes in fibrosis-related proteins, while this protective effect was blocked by ML385. Conclusion IPA ameliorates renal fibrosis by activating the Nrf2 pathway, offering a potential therapeutic strategy for renal injury.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147909833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

USP18 reduces the inflammatory response of LPS-induced SA-AKI by inhibiting the PI3K-AKT-NF-κB pathway and regulate apoptosis of cells USP18通过抑制PI3K-AKT-NF-κB通路，降低lps诱导的SA-AKI的炎症反应，调控细胞凋亡

4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2024-09-09 DOI: 10.1177/14703203241265218

Yang Chong, Xue-ying Wu, Yiqi Wang, Quan-kuan Gu, Jiannan Zhang, Xianglin Meng, Yue Li, Wei Yang, Nana Li, Huanhuan Liu, Qianqian Gao, Mingyan Zhao

{"title":"USP18 reduces the inflammatory response of LPS-induced SA-AKI by inhibiting the PI3K-AKT-NF-κB pathway and regulate apoptosis of cells","authors":"Yang Chong, Xue-ying Wu, Yiqi Wang, Quan-kuan Gu, Jiannan Zhang, Xianglin Meng, Yue Li, Wei Yang, Nana Li, Huanhuan Liu, Qianqian Gao, Mingyan Zhao","doi":"10.1177/14703203241265218","DOIUrl":"https://doi.org/10.1177/14703203241265218","url":null,"abstract":"Background Sepsis-associated acute kidney injury (SA-AKI) is marked by systemic inflammation and organ dysfunction. Ubiquitin-specific protease 18 (USP18) is a regulator in immune responses and apoptosis. Objectives To explore USP18's role in inflammatory pathways and apoptosis in SA-AKI, particularly its interactions with the PI3K-AKT-NF-κB pathway. Design A combination of animal experiments and cellular models was employed to investigate the expression and regulatory functions of USP18 in both in vivo and in vitro settings. Methods We established SA-AKI models in mice and HK-2 cells using LPS. Gene expression was analyzed via RNA-seq, and Cr, BUN, and inflammatory factors were measured using biochemical assays and ELISA. Kidney pathology was assessed with HE staining, mRNA levels with qRT-PCR, protein expression with Western blots, and cell apoptosis with flow cytometry. Results In SA-AKI mice model and HK-2 cell lines, upregulated USP18 was linked to increased activity in the PI3K-AKT-NF-κB pathway and heightened inflammation. Conversely, USP18 downregulation decreased early cell apoptosis and raised levels of inflammatory proteins. Elevated USP18 levels were also found in SA-AKI patients’ blood and urine. Conclusion USP18 enhances in vitro and in vivo responses by modulating inflammation and apoptosis through the PI3K-AKT-NF-κB pathway, presenting a potential target for SA-AKI therapy.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147912517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of COVID-19: A Meta-Analysis. 血管紧张素转换酶插入/缺失多态性与COVID-19风险的关系:一项荟萃分析

IF 2.9 4区医学

Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2023-11-28 eCollection Date: 2023-01-01 DOI: 10.1155/2023/3431612

Hu Luoyi, Pan Yan, Fan Qihong

{"title":"Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of COVID-19: A Meta-Analysis.","authors":"Hu Luoyi, Pan Yan, Fan Qihong","doi":"10.1155/2023/3431612","DOIUrl":"10.1155/2023/3431612","url":null,"abstract":"Introduction: Research shows the correlation between angiotensin-converting enzyme (ACE) deletion and insertion (D/I) polymorphism and COVID-19 risk; yet, conclusive evidence is still lacking. Thus, a meta-analysis of relevant articles was performed to more accurately estimate the relationship of ACE I/D polymorphism with the risk of COVID-19. Material and Methods. Relevant literature from the PubMed database was systematically reviewed, and odds ratios (ORs) and associated 95% confidence intervals (CIs) were measured. Additionally, the metapackage from Stata version 15.0 was used for statistical analysis.Results: The meta-analysis eventually contained 8 studies, including 1362 COVID-19 cases and 4312 controls. Based on the data, the ACE I/D polymorphism did not show an association with COVID-19 risk (D vs. I: OR = 1.25, 95% CI = 0.96-1.64; DD vs. II: OR = 1.89, 95% CI = 0.95-3.74; DI vs. II: OR = 1.75, 95% CI = 0.92-3.31; dominant model: OR = 1.88, 95% CI = 0.99-3.53; and recessive model: OR = 1.24, 95% CI = 0.81-1.90). Further, subgroup analyses stratified based on case proved that the ACE D allele demonstrated an association with increasing risk of COVID-19 severity (D vs. I: OR = 1.64, 95% CI = 1.01-2.66; DD vs. II: OR = 4.62, 95% CI = 2.57-8.30; DI vs. II: OR = 3.07, 95% CI = 1.75-5.38; dominant model: OR = 3.74, 95% CI = 2.15-6.50; and recessive model: OR = 1.28, 95% CI = 0.46-3.51).Conclusions: The ACE D allele was clearly related to an enhanced risk of COVID-19 severity. Hence, it is imperative to take into account the influence of genetic factors during the development of future vaccines.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"2023 ","pages":"3431612"},"PeriodicalIF":2.9,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0