| 1. |
- Zhang, Xiaoying, et al.
(författare)
-
IL-6 Regulates MMP-10 Expression via JAK2/STAT3 Signaling Pathway in a Human Lung Adenocarcinoma Cell Line
- 2009
-
Ingår i: Anticancer research. - 1791-7530. ; 29:11, s. 4497-4501
-
Tidskriftsartikel (refereegranskat)abstract
- We previously reported that matrix metalloproteinase (MMP)-10 mRNA levels were significantly lower in tumor tissues than in adjacent normal tissues in human non-small cell lung cancer (NSCLC), whereas protein levels of MMP-10 were higher in the tumor tissues than the adjacent tissues. The mechanism of this divergence is still unknown. In the present stud), the role of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) on interleukin (IL)-6 mediated regulation of MMP-10 expression was investigated in a human lung adenocarcinoma cell line (A549 cells) and the molecular regulatory mechanism of MMP-10 expression was explored. A549 cells were stimulated by different concentrations of IL-6 with or without AG490, a specific JAK2 inhibitor. It was demonstrated that IL-6 moderately reduced the MMP-10 mRNA levels, whereas it significantly enhanced the MMP-10 protein mass in the A549 cells. This phenomenon mimicked the divergence of mRNA level and protein mass of MMP-10 in human NSCLC. Moreover, the present study indicated that IL-6 regulation of MMP-10 expression was via the JAK2/STAT3 pathway. STAT3 mRNA levels were significantly increased when the cells were treated with IL-6, whereas when AG490 (50 mu M) was added to the cell cultures, IL-6-induced increase of STAT3 mRNA levels was abolished. Meanwhile, AG490 blocked the IL-6-induced inhibition of MMP-10 mRNA as well as blocking the IL-6-induced increase of MMP-10 protein mass in the A549 cells. Neither IL-6 nor AG490 influenced JAK2 mRNA levels in the A549 cell cultures. It is concluded that the JAK2/STAT3 pathway is involved in the IL-6-mediated regulation of MMP-10, and IL-6 can moderately reduce MMP-10 mRNA levels and strongly increase MMP-10 protein mass in human lung adenocarcinoma A549 cells. Contrasting effects of IL-6 on MMP-10 mRNA level and protein concentration in A549 cells may partially explain the divergence of MMP-10 mRNA level and protein mass in human NSCLC.
|
|
| 2. |
- Luo, Guanghua, et al.
(författare)
-
Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPARβ/δ in HepG2 cells.
- 2014
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 445:1, s. 203-207
-
Tidskriftsartikel (refereegranskat)abstract
- It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPARβ/δ pathway.
|
|
| 3. |
- Luo, Guanghua, et al.
(författare)
-
Rosiglitazone Enhances Apolipoprotein M (Apom) Expression in Rat's Liver.
- 2014
-
Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 11:10, s. 1015-1021
-
Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of high density lipoprotein (HDL), which plays a crucial role behind the mechanism of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin resistance could associate with decreased APOM expressions. In agreement with our previous reports, here, we further confirmed that the insulin sensitivity was also reduced in rats treated with high concentrations of glucose; such effect could be reversed by administration of rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ). The present study shows that Apom expression is significantly affected by either rosiglitazone or hyperglycemia alone without cross interaction with each other, which indicates that the pathway of Apom expression regulating by hyperglycemia might be differed from that by rosiglitazone. Further study indicated that hyperglycemia could significantly inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1) (P<0.0001), liver receptor homologue-1 (Lrh1) (P=0.0012), ATP-binding cassette transporter 1 (Abca1) (P=0.0012) and Pparb/d (P=0.0043). Two-way ANOVA analysis demonstrated that the interactions between rosiglitazone and infusion of 25% glucose solution on Shp1 (P=0.0054) and Abca1 (4E, P=0.0004) mRNA expression was statistically significant. It is concluded that rosiglitazone could increase Apom expression, of which the detailed mechanism needs to be further investigated. The downregulation of Apom by hyperglycemia might be mainly through decreasing expression of Pparg and followed by inhibiting Lxrb in rats.
|
|
| 4. |
- Shi, Yuanping, et al.
(författare)
-
Comprehensive lipidomics in apoM−/− mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation
- 2020
-
Ingår i: Journal of Genetics and Genomics. - : Elsevier BV. - 1673-8527. ; 47:9, s. 523-534
-
Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apoM affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apoM on liver and plasma lipidomes and how apoM participates in lipid cycling, via apoM knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry–based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters (CEs), in apoM−/− mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apoM−/− mice; while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of ApoB-100 was dramatically increased in the liver, whereas significant reductions in both ApoB-100 and low-density lipoprotein (LDL) cholesterol were observed in the serum of apoM−/− mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apoM−/− leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apoM knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.
|
|
| 5. |
- Zheng, Lu, et al.
(författare)
-
Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.
- 2014
-
Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 11:4, s. 365-372
-
Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.
|
|
| 6. |
- Zheng, Lu, et al.
(författare)
-
Intralipid decreases apolipoprotein m levels and insulin sensitivity in rats.
- 2014
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (ApoM) is a constituent of high-density lipoproteins (HDL). It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels.
|
|
| 7. |
- Shi, Yuanping, et al.
(författare)
-
Expression of Zinc Finger 23 Gene in Human Hepatocellular Carcinoma
- 2011
-
Ingår i: Anticancer research. - 1791-7530. ; 31:10, s. 3595-3599
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the relationship between human zinc finger 23 (ZNF23) expression and clinico-pathological characteristics in patients suffering from hepatocellular carcinoma (HCC), and to investigate ZNF23 expression in relation to cell apoptosis. Patients and Methods: Thirty-seven HCC samples were collected and ZFP23 mRNA levels were determined by real-time reverse transcription-polymerase chain reaction (RTPCR). Correlation between ZNF23 expression and patients' clinical characteristics was analyzed. For determining the effect of ZNF23 on cell apoptosis, HepG2 cells were exposed to cisplatin at different concentrations and ZNF23 mRNA assayed. Results: Median relative mRNA levels of ZNF23 mRNA in HCC tissues and adjacent tissues were 8.84 (3.59-15.05) and 22.20 (13.85-42.90), respectively (U=259.5, p<0.01). Median mRNA levels of ZNF23 in patients with Edmondson stage I+II disease [12.80 (4.80-19.50)] were much higher than those of patients with stage III+IV disease [5.01 (2.88-11.68), U=99.00, p<0.05]. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that cisplatin significantly inhibited cell proliferation of HepG2 cells in a dose-dependent manner, which was positively correlated to cell apoptosis (F=27.89, p<0.01), and in response to increasing cisplatin concentrations, ZNF23 mRNA levels increased in the cells. Conclusion: Cisplatin-induced apoptotic effect in HepG2 cells may be mediated via the up-regulation of ZNF23, which suggests that the ZNF23 gene could play an important role in the development of hepatocellular carcinoma.
|
|
| 8. |
- Yao, Shuang, et al.
(författare)
-
Insulin resistance in apolipoprotein M knockout mice is mediated by the protein kinase akt signaling pathway
- 2020
-
Ingår i: Endocrine, Metabolic & Immune Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5303. ; 20:5, s. 771-780
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous clinical studies have suggested that apolipoprotein M (apoM) is involved in glucose metabolism and plays a causative role in insulin sensitivity. Objective: The potential mechanism of apoM on modulating glucose homeostasis is explored and differentially expressed genes are analyzed by employing ApoM deficient (ApoM-/-) and wild type (WT) mice. Methods: The metabolism of glucose in the hepatic tissues of high-fat diet ApoM-/- and WT mice was measured by a glycomics approach. Bioinformatic analysis was applied for analyzing the levels of differentially expressed mRNAs in the liver tissues of these mice. The insulin sensitivity of ApoM-/- and WT mice was compared using the insulin tolerance test and the phosphorylation levels of protein kinase Akt (AKT) and insulin stimulation in different tissues were examined by Western blot. Results: The majority of the hepatic glucose metabolites exhibited lower concentration levels in the ApoM-/- mice compared with those of the WT mice. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that ApoM deficiency affected the genes associated with the metabolism of glucose. The insulin tolerance test suggested that insulin sensitivity was impaired in ApoM-/- mice. The phosphorylation levels of AKT in muscle and adipose tissues of ApoM-/- mice were significantly diminished in response to insulin stimulation compared with those noted in WT mice. Conclusion: ApoM deficiency led to the disorders of glucose metabolism and altered genes related to glucose metabolism in mice liver. In vivo data indicated that apoM might augment insulin sensitivity by AKT-dependent mechanism.
|
|
