Lipopolysaccharide-Induced Transcriptional Changes in LBP-Deficient Rat and Its Possible Implications for Liver Dysregulation during Sepsis.
Lipopolysaccharide-Induced Transcriptional Changes in LBP-Deficient Rat and Its Possible Implications for Liver Dysregulation during Sepsis.
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DOI：
10.1155/2021/8356645
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发表时间：
2021
影响因子：
4.1
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
He Z;Song Z;Meng L;Cheng W;Huang F;Zheng M;Xu W;Xiao R;Fang H;Zhu Y
脓毒症是由对感染的炎症反应失调引起的器官功能障碍。脂多糖结合蛋白（LBP）与脂多糖（LPS）结合并调节炎症反应。迄今为止，关于LBP基因在LPS诱导的脓毒症中的作用的系统研究尚未见报道。在此，我们探索了RNA测序技术，以描绘LBP缺陷大鼠和WT大鼠在LPS给药后多个时间点的肝组织转录组学变化。我们进行肝组织RNA测序，以寻找差异表达的基因（DEG）和丰富的生物学过程和途径之间的WT和LBP缺陷组在0小时，6小时，24小时。总共在0 h、6 h和24 h分别鉴定了168、284和307个DEG，包括Lrp 5、Cyp 7a 1、Nfkbiz、Sigmar 1、Fabp 7和Hao 1，它们与炎症或脂质相关过程相关。功能富集分析显示，由Ifng，Cxcl 10，Serpine 1和Lbp介导的对LPS的炎症反应在6 h时增强，而与C5，Cyp 4a 1和Eci 1相关的脂质相关代谢在LPS给药后24 h时在WT样品中富集。当LBP基因被敲除时，未发现炎症过程; LBP缺陷样品中脂质相关代谢过程和由Dhrs 7 b和Tysnd 1介导的过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体，过氧化物酶体增殖物激活受体）信号通路被显著激活。我们的研究提示，LPS可能通过与LBP相互作用，激活核因子-κ B（NF-κB）信号通路，引发炎症反应。而在LBP基因缺失的情况下，脂质相关代谢在抑制NF-κB活性的同时，会通过影响PPAR信号通路而使细菌清除。采用生化分析仪检测血清乳酸脱氢酶（LDH）和碱性磷酸酶（ALP）水平，免疫组化法检测血清高迁移率族蛋白B1（HMGB 1）和切割型半胱氨酸蛋白酶3（cleaved-caspase 3）的表达，进一步验证上述结论。
Sepsis is an organ dysfunction caused by the dysregulated inflammatory response to infection. Lipopolysaccharide-binding protein (LBP) binds to lipopolysaccharide (LPS) and modulates the inflammatory response. A rare systematic study has been reported to detect the effect of LBP gene during LPS-induced sepsis. Herein, we explored the RNA sequencing technology to profile the transcriptomic changes in liver tissue between LBP-deficient rats and WT rats at multiple time points after LPS administration. We proceeded RNA sequencing of liver tissue to search differentially expressed genes (DEGs) and enriched biological processes and pathways between WT and LBP-deficient groups at 0 h, 6 h, and 24 h. In total, 168, 284, and 307 DEGs were identified at 0 h, 6 h, and 24 h, respectively, including Lrp5, Cyp7a1, Nfkbiz, Sigmar1, Fabp7, and Hao1, which are related to the inflammatory or lipid-related process. Functional enrichment analysis revealed that inflammatory response to LPS mediated by Ifng, Cxcl10, Serpine1, and Lbp was enhanced at 6 h, while lipid-related metabolism associated with C5, Cyp4a1, and Eci1 was enriched at 24 h after LPS administration in the WT samples. The inflammatory process was not found when the LBP gene was knocked out; lipid-related metabolic process and peroxisome proliferator-activated receptor (PPAR) signaling pathway mediated by Dhrs7b and Tysnd1 were significantly activated in LBP-deficient samples. Our study suggested that the invading LPS may interplay with LBP to activate the nuclear factor kappa B (NF-κB) signaling pathway and trigger uncontrolled inflammatory response. However, when inhibiting the activity of NF-κB, lipid-related metabolism would make bacteria removal via the effect on the PPAR signaling pathway in the absence of LBP gene. We also compared the serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels using the biochemistry analyzer and analyzed the expression of high mobility group box 1 (HMGB1) and cleaved-caspase 3 with immunohistochemistry, which further validated our conclusion.
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影响因子：
3.7
作者：
Liu A;Fang H;Dirsch O;Jin H;Dahmen U
通讯作者：
Dahmen U
DOI：
10.1097/shk.0000000000000520
发表时间：
2016-04
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Araújo CV;Campbell C;Gonçalves-de-Albuquerque CF;Molinaro R;Cody MJ;Yost CC;Bozza PT;Zimmerman GA;Weyrich AS;Castro-Faria-Neto HC;Silva AR
通讯作者：
Silva AR
黄芩素通过抑制小鼠炎症和细胞凋亡来防止多种微生物脓毒症引起的肝损伤。
影响因子：
5
作者：
Liu, Anding;Wang, Wenjie;Dirsch, Olaf
通讯作者：
Dirsch, Olaf
影响因子：
32.4
作者：
Eckert, Jana K.;Kim, Young J.;Schumann, Ralf R.
通讯作者：
Schumann, Ralf R.
DOI：
10.1186/s12950-018-0197-4
发表时间：
2018
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Fang H;Liu A;Chen X;Cheng W;Dirsch O;Dahmen U
通讯作者：
Dahmen U