Lipid metabolism participates in human membranous nephropathy identified by whole-genome gene expression profiling

2019 ◽  
Vol 133 (11) ◽  
pp. 1255-1269
Author(s):  
Di Wu ◽  
Zhenxiang Yu ◽  
Songchen Zhao ◽  
Zhihui Qu ◽  
Weixia Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Lipid Metabolism ◽  
Membranous Nephropathy ◽  
Expression Profiling ◽  
Acid Metabolism ◽  
Renal Cortex ◽  
Cholesterol Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Whole Genome

Abstract A genomics approach is an effective way to understand the possible mechanisms underlying the onset and progression of disease. However, very limited results have been published regarding whole-genome expression analysis of human idiopathic membranous nephropathy (iMN) using renal tissue. In the present study, gene expression profiling using renal cortex tissue from iMN patients and healthy controls was conducted; differentially expressed genes (DEGs) were filtered out, and 167 up- and 291 down-regulated genes were identified as overlapping DEGs (ODEGs). Moreover, enrichment analysis and protein–protein network construction were performed, revealing enrichment of genes mainly in cholesterol metabolism and arachidonic acid metabolism, among others, with 38 hub genes obtained. Furthermore, we found several associations between circulating lipid concentrations and hub gene signal intensities in the renal cortex. Our findings indicate that lipid metabolism, including cholesterol metabolism and arachidonic acid metabolism, may participate in iMN pathogenesis through key genes, including apolipoprotein A1 (APOA1), apolipoprotein B (APOB), apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP), and phospholipase A2 group XIIB (PLA2G12B).

scholarly journals Cholera toxin induces expression of the immediate-early response gene JE via a cyclic AMP-independent signaling pathway.

1991 ◽  
Vol 11 (1) ◽  
pp. 102-107 ◽  
Author(s):  
S A Qureshi ◽  
K Alexandropoulos ◽  
C K Joseph ◽  
R Spangler ◽  
D A Foster
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Cholera Toxin ◽  
Signaling Pathway ◽  
Acid Metabolism ◽  
Early Response ◽  
Arachidonic Acid Metabolism ◽  
Immediate Early

Cholera toxin (CT) activates expression of two immediate-early response genes (JE and TIS10) in quiescent BALB/c 3T3 cells. Increases in cyclic AMP (cAMP) levels in response to CT are likely responsible for the induction of TIS10 gene expression, since treatment with 8-Br-cAMP and increasing the intracellular levels of cAMP by treatment with forskolin induce TIS10 gene expression. In contrast, neither forskolin nor 8-Br-cAMP induces JE gene expression. 3-Isobutyl-1-methylxanthine, which stabilizes intracellular cAMP, potentiates CT-induced TIS10 gene expression but has no effect on CT-induced JE gene expression. Thus, induction of JE by CT is independent of the cAMP produced in response to CT. Induction of JE by CT does not require protein kinase C (PKC), since depleting cells of PKC activity has no effect on the induction of JE by CT. CT-induced expression of JE can be distinguished from CT-induced TIS10 gene expression by using protein kinase inhibitors and inhibitors of arachidonic acid metabolism, further suggesting distinct signaling pathways for CT-induced JE and TIS10 gene expression. Thus, induction of JE gene expression by CT results from the activation of an intracellular signaling pathway that is independent of cAMP production. This pathway is independent of PKC activity and uniquely sensitive to inhibitors of protein kinases and arachidonic acid metabolism.

Changes in amniotic arachidonic acid metabolism associated with increased cyclo-oxygenase gene expression

1993 ◽  
Vol 100 (11) ◽  
pp. 1037-1042 ◽  
Author(s):  
Phillip R. Bennett ◽  
Donna Slater ◽  
Mark Sullivan ◽  
Murdoch G. Elder ◽  
Gudrun E. Moore
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism

Cholera toxin induces expression of the immediate-early response gene JE via a cyclic AMP-independent signaling pathway

1991 ◽  
Vol 11 (1) ◽  
pp. 102-107
Author(s):  
S A Qureshi ◽  
K Alexandropoulos ◽  
C K Joseph ◽  
R Spangler ◽  
D A Foster
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Cholera Toxin ◽  
Signaling Pathway ◽  
Acid Metabolism ◽  
Early Response ◽  
Arachidonic Acid Metabolism ◽  
Immediate Early

Cholera toxin (CT) activates expression of two immediate-early response genes (JE and TIS10) in quiescent BALB/c 3T3 cells. Increases in cyclic AMP (cAMP) levels in response to CT are likely responsible for the induction of TIS10 gene expression, since treatment with 8-Br-cAMP and increasing the intracellular levels of cAMP by treatment with forskolin induce TIS10 gene expression. In contrast, neither forskolin nor 8-Br-cAMP induces JE gene expression. 3-Isobutyl-1-methylxanthine, which stabilizes intracellular cAMP, potentiates CT-induced TIS10 gene expression but has no effect on CT-induced JE gene expression. Thus, induction of JE by CT is independent of the cAMP produced in response to CT. Induction of JE by CT does not require protein kinase C (PKC), since depleting cells of PKC activity has no effect on the induction of JE by CT. CT-induced expression of JE can be distinguished from CT-induced TIS10 gene expression by using protein kinase inhibitors and inhibitors of arachidonic acid metabolism, further suggesting distinct signaling pathways for CT-induced JE and TIS10 gene expression. Thus, induction of JE gene expression by CT results from the activation of an intracellular signaling pathway that is independent of cAMP production. This pathway is independent of PKC activity and uniquely sensitive to inhibitors of protein kinases and arachidonic acid metabolism.

scholarly journals Metformin Affects Cardiac Arachidonic Acid Metabolism and Cardiac Lipid Metabolite Storage in a Prediabetic Rat Model

2021 ◽  
Vol 22 (14) ◽  
pp. 7680
Author(s):  
Denisa Miklankova ◽  
Irena Markova ◽  
Martina Hüttl ◽  
Iveta Zapletalova ◽  
Martin Poruba ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Rat Model ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Phospholipid Fatty Acid Composition ◽  
Metformin Treatment ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites

Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids—triglycerides, cholesteryl esters and the lipotoxic intermediates—diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.

scholarly journals Mechanism of Curcuma wenyujin Rhizoma on Acute Blood Stasis in Rats Based on a UPLC-Q/TOF-MS Metabolomics and Network Approach

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 82 ◽  
Author(s):  
Min Hao ◽  
De Ji ◽  
Lin Li ◽  
Lianlin Su ◽  
Wei Gu ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Acid Metabolism ◽  
Blood Stasis ◽  
Arachidonic Acid Metabolism ◽  
Sphingolipid Metabolism ◽  
Network Pharmacology ◽  
Therapeutic Mechanism ◽  
Linoleic Acid Metabolism

Rhizome of Curcuma wenyujin, which is called EZhu in China, is a traditional Chinese medicine used to treat blood stasis for many years. However, the underlying mechanism of EZhu is not clear at present. In this study, plasma metabolomics combined with network pharmacology were used to elucidate the therapeutic mechanism of EZhu in blood stasis from a metabolic perspective. The results showed that 26 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees by EZhu preadministration. Metabolic pathway analysis showed that the improvement of blood stasis by Curcuma wenyujin rhizome was mainly related to lipid metabolism (linoleic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism) and amino acid metabolisms (tryptophan metabolism, lysine degradation). The component-target-pathway network showed that 68 target proteins were associated with 21 chemical components in EZhu. Five metabolic pathways of the network, including linoleic acid metabolism, sphingolipid metabolism, glycerolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis, were consistent with plasma metabolomics results. In conclusion, plasma metabolomics combined with network pharmacology can be helpful to clarify the mechanism of EZhu in improving blood stasis and to provide a literature basis for further research on the therapeutic mechanism of EZhu in clinical practice.

scholarly journals The Rumen Microbiome and Its Metabolome Together With the Host Transcriptome Act to Regulate the Cold Season Adaptation Mechanism of Grazing Tibetan Sheep

2021 ◽  
Author(s):  
Xiu Liu ◽  
Yuzhu Sha ◽  
Weibing Lv ◽  
Xinyu Guo ◽  
Xiaoning Pu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Acid Metabolism ◽  
Cold Season ◽  
Arachidonic Acid Metabolism ◽  
Tibet Plateau ◽  
Rumen Epithelium ◽  
Tibetan Sheep ◽  
Metabolism Of Xenobiotics

Abstract BackgroundTibetan sheep are important ruminants on the Qinghai-Tibet Plateau. They can maintain a normal life and reproduce in harsh environments under extreme cold and low oxygen. However, the molecular and metabolic mechanisms underlying the adaptability of Tibetan sheep during the cold season are still unclear. Hence, we conducted a comprehensive analysis of rumen epithelial morphology, epithelial transcriptomics, microbiology and metabolomics in a Tibetan sheep model to understand the interaction between the rumen host and microbiota and their metabolites and to explore the potential regulatory mechanism of Tibetan sheep adaptability to the cold season of the plateau. ResultsMorphological analysis showed that the ruminal muscle layer thickness and nipple width of Tibetan sheep increased significantly during the cold season ( P <0.05), and the thickness of the stratum corneum, stratum granulosa and stratum spinous of the rumen epithelium increased significantly ( P <0.05). Transcriptomics analysis showed that the differential genes were primarily enriched in the PPAR signaling pathway (ko03320), legionellosis (ko05134), phagosome (ko04145), arginine and proline metabolism (ko00330), and metabolism of xenobiotics by cytochrome P450 (ko00980). Unique differential metabolites were identified in cold season, such as cynaroside A, sanguisorbin B and tryptophyl-valine, which were mainly enriched in arachidonic acid metabolism, arachidonic acid metabolism and linolenic acid metabolism pathways, and had certain correlation with microorganisms. Integrated transcriptome-metabolome-microbiome analysis showed that epithelial gene- GSTM3 expression was upregulated in the metabolism of xenobiotics by the cytochrome P450 pathway during the cold season, leading to the downregulation of some harmful metabolites; TLR5 gene expression was upregulated and CD14 gene expression was downregulated in the legionellosis pathway during the cold season. A large number of metabolites, such as glucosidic acid and vitamin A, were produced in the steroid hormone biosynthesis and retinol metabolism pathways. ConclusionThis study comprehensively described the interaction mechanism between the rumen host and microbes and their metabolites in grazing Tibetan sheep during the cold season. Under the stimulation of the cold plateau environment, the morphological structure of the rumen epithelium of Tibetan sheep undergoes adaptive changes. Rumen epithelial genes, microbiota and metabolites act together in some key pathways related to cold season adaptation.

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