AFM negatively regulates the infiltration of monocytes to mediate sepsis-associated acute kidney injury.
AFM negatively regulates the infiltration of monocytes to mediate sepsis-associated acute kidney injury.
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AFM 负向调节单核细胞浸润介导脓毒症相关急性肾损伤
DOI：
10.3389/fimmu.2023.1049536
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发表时间：
2023
影响因子：
7.3
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
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作者：
Guo, Caiyun;Fan, Youling;Cheng, Jiurong;Deng, Yingdong;Zhang, Xiangsheng;Chen, Yanna;Jing, Huan;Li, Wenjun;Liu, Pei;Xie, Jiaqi;Ning, Wenjun;Chen, Hongtao;Zhou, Jun
脓毒症是由于宿主对感染的有害反应而导致的器官功能障碍，而肾脏是常见脓毒症中受损的器官之一。脓毒症相关急性肾损伤（SA-AKI）增加脓毒症患者的死亡率。虽然大量的研究已经改善了疾病的预防和治疗，但SA-SKI仍然是一个重要的临床问题。目的利用加权基因共表达网络分析（WGCNA）和免疫浸润分析研究SA-AKI相关的诊断标志物和潜在的治疗靶点。对来自基因表达合成（GEO）数据库的SA-AKI表达数据集进行免疫渗透分析。对作为性状数据的免疫侵袭得分进行加权基因共表达网络分析（WGCNA），并且将与感兴趣的免疫细胞相关的模块鉴定为中枢模块。使用蛋白质-蛋白质相互作用（PPI）网络分析筛选枢纽模块中的枢纽基因。通过与通过差异表达分析筛选的显著不同的基因交叉，将枢纽基因鉴定为靶标，并使用两个外部数据集进行验证。最后，实验验证了目的基因SA-AKI与免疫细胞之间的相关性。使用WGCNA和免疫浸润分析鉴定与单核细胞相关的绿色模块。差异表达分析和PPI网络分析确定了两个枢纽基因（AFM和GSTA 1）。使用其他阿基数据集GSE 30718和GSE 44925进行的进一步验证表明，AFM在阿基样品中显著下调，并与阿基的发展相关。枢纽基因与免疫细胞的相关性分析表明，AFM与单核细胞浸润显著相关，因此被选为关键基因。此外，基因单富集分析（GSEA）和PPI分析结果表明，原子力显微镜与SA-AKI的发生发展显著相关。 AFM与阿基肾脏中单核细胞的募集和各种炎症因子的释放呈负相关。AFM可作为脓毒症相关阿基中单核细胞浸润的潜在生物标志物和治疗靶点。
Sepsis is organ dysfunction due to the host’s deleterious response to infection, and the kidneys are one of the organs damaged in common sepsis. Sepsis-associated acute kidney injury (SA-AKI) increases the mortality in patients with sepsis. Although a substantial volume of research has improved the prevention and treatment of the disease, SA-SKI is still a significant clinical concern. Aimed to use weighted gene co-expression network analysis (WGCNA) and immunoinfiltration analysis to study SA-AKI-related diagnostic markers and potential therapeutic targets. Immunoinfiltration analysis was performed on SA-AKI expression datasets from the Gene Expression Synthesis (GEO) database. A weighted gene co-expression network analysis (WGCNA) analysis was performed on immune invasion scores as trait data, and modules associated with immune cells of interest were identified as hub modules. Screening hub geneset in the hub module using protein-protein interaction (PPI) network analysis. The hub gene was identified as a target by intersecting with significantly different genes screened by differential expression analysis and validated using two external datasets. Finally, the correlation between the target gene, SA-AKI, and immune cells was verified experimentally. Green modules associated with monocytes were identified using WGCNA and immune infiltration analysis. Differential expression analysis and PPI network analysis identified two hub genes (AFM and GSTA1). Further validation using additional AKI datasets GSE30718 and GSE44925 showed that AFM was significantly downregulated in AKI samples and correlated with the development of AKI. The correlation analysis of hub genes and immune cells showed that AFM was significantly associated with monocyte infiltration and hence, selected as a critical gene. In addition, Gene single-enrichment analysis (GSEA) and PPI analyses results showed that AFM was significantly related to the occurrence and development of SA-AKI. AFM is inversely correlated with the recruitment of monocytes and the release of various inflammatory factors in the kidneys of AKI. AFM can be a potential biomarker and therapeutic target for monocyte infiltration in sepsis-related AKI.
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影响因子：
7.3
作者：
Horiguchi H;Loftus TJ;Hawkins RB;Raymond SL;Stortz JA;Hollen MK;Weiss BP;Miller ES;Bihorac A;Larson SD;Mohr AM;Brakenridge SC;Tsujimoto H;Ueno H;Moore FA;Moldawer LL;Efron PA;Sepsis and Critical Illness Research Center Investigators
通讯作者：
Sepsis and Critical Illness Research Center Investigators
影响因子：
7.7
作者：
Janosevic D;Myslinski J;McCarthy TW;Zollman A;Syed F;Xuei X;Gao H;Liu YL;Collins KS;Cheng YH;Winfree S;El-Achkar TM;Maier B;Melo Ferreira R;Eadon MT;Hato T;Dagher PC
通讯作者：
Dagher PC
影响因子：
5.5
作者：
Juhász I;Ujfalusi S;Seres I;Lőrincz H;Varga VE;Paragh G Jr;Somodi S;Harangi M;Paragh G
通讯作者：
Paragh G
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.6
作者：
通讯作者：
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