Biomedical subjects

Jose M Mato

Publications and source records attributed to Jose M Mato.

5 recordsLinked to original sources

PubMed2025

Interplay among lipoprotein(a), hepatic and vascular damage in individuals with metabolic dysfunction.

BACKGROUND: The relationship between plasma lipoprotein(a) [Lp(a)] levels and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. The aim of this study was to examine the combined effects of Lp(a) levels on liver and vascular damage. METHODS: The study was conducted using the Liver-Bible cohort of individuals with metabolic dysfunction (n = 859, 808 with genomic information) and the Milan Biobank (n = 6963). Genome-wide association studies (GWAS) and polygenic risk scores (PRS) were used to evaluate the inherited factors influencing plasma Lp(a) levels. RESULTS: In the Liver-Bible cohort, genetic variation in the LPA gene was the strongest determinant of Lp(a), followed by liver stiffness measurement (LSM). Additionally, circulating Lp(a) levels, but not genetic predisposition, were inversely related to LSM, suggesting that MASLD severity may affect Lp(a) secretion. Among participants with more severe insulin resistance (n = 250), Lp(a) levels (odds ratio 6.7, 95% CI 1.0-53.0, p = 0.046) and LSM (odds ratio 13.7, 95% CI 1.4-172.2, p = 0.023) were associated with greater prevalence of carotid atherosclerotic plaques, regardless of traditional cardiovascular risk factors. In the Milan Biobank, genetically predicted higher Lp(a) levels tended to increase the risk of liver-related outcomes, whereas genetically predicted MASLD was associated with lower circulating Lp(a) levels. CONCLUSIONS: The results of this study suggest that liver damage is more likely the cause of reduced plasma Lp(a) levels rather than a consequence. Assessing plasma Lp(a) levels and the extent of liver damage could improve the prediction of vascular damage.

Humans↗

PubMed2004

Inhibition of lipopolysaccharide-stimulated TNF-alpha promoter activity by S-adenosylmethionine and 5'-methylthioadenosine.

S-adenosylmethionine (SAM) is the principal biological methyl donor and precursor for polyamines. SAM is known to be hepatoprotective in many liver disease models in which TNF-alpha is implicated. The present study investigated whether and how SAM inhibited LPS-stimulated TNF-alpha expression in Kupffer cells (hepatic macrophages). SAM downregulated TNF-alpha expression in LPS-stimulated Kupffer cells at the transcriptional level as suggested by a transfection experiment with a TNF-alpha promoter-reporter gene. This inhibition was not mediated through decreased NF-kappaB binding to four putative kappaB binding elements located within the promoter. The inhibited promoter activity was neither prevented by overexpression of p65 and/or its coactivator p300 nor enhanced by overexpression of coactivator-associated arginine methyltransferase-1, an enzyme that methylates p300 and inhibits a p65-p300 interaction. SAM did not lead to DNA methylation at the most common CpG target sites in the TNF-alpha promoter. Moreover, 5'-methylthioadenosine (MTA), which is derived from SAM but does not serve as a methyl donor, recapitulated SAM's effect with more potency. These data demonstrate that SAM inhibits TNF-alpha expression at the level downstream of NF-kappaB binding and at the level of the promoter activity via mechanisms that do not appear to involve the limited availability of p65 or p300. Furthermore, our study is the first to demonstrate a potent inhibitory effect on NF-kappaB promoter activity and TNF-alpha expression by a SAM's metabolite, MTA.

Animals↗

PubMed2003

GARBAN: genomic analysis and rapid biological annotation of cDNA microarray and proteomic data.

SUMMARY: Genomic Analysis and Rapid Biological ANnotation (GARBAN) is a new tool that provides an integrated framework to analyze simultaneously and compare multiple data sets derived from microarray or proteomic experiments. It carries out automated classifications of genes or proteins according to the criteria of the Gene Ontology Consortium at a level of depth defined by the user. Additionally, it performs clustering analysis of all sets based on functional categories or on differential expression levels. GARBAN also provides graphical representations of the biological pathways in which all the genes/proteins participate. AVAILABILITY: http://garban.tecnun.es.

Algorithms↗

PubMed2002

S-Adenosylmethionine: a control switch that regulates liver function.

Genome sequence analysis reveals that all organisms synthesize S-adenosylmethionine (AdoMet) and that a large fraction of all genes is AdoMet-dependent methyltransferases. AdoMet-dependent methylation has been shown to be central to many biological processes. Up to 85% of all methylation reactions and as much as 48% of methionine metabolism occur in the liver, which indicates the crucial importance of this organ in the regulation of blood methionine. Of the two mammalian genes (MAT1A, MAT2A) that encode methionine adenosyltransferase (MAT, the enzyme that makes AdoMet), MAT1A is specifically expressed in adult liver. It now appears that growth factors, cytokines, and hormones regulate liver MAT mRNA levels and enzyme activity and that AdoMet should not be viewed only as an intermediate metabolite in methionine catabolism, but also as an intracellular control switch that regulates essential hepatic functions such as regeneration, differentiation, and the sensitivity of this organ to injury. The aim of this review is to integrate these recent findings linking AdoMet with liver growth, differentiation, and injury into a comprehensive model. With the availability of AdoMet as a nutritional supplement and evidence of its beneficial role in various liver diseases, this review offers insight into its mechanism of action.

Animals↗

PubMedDate not supplied

Anti-inflammatory effects of hepatocyte growth factor: induction of interleukin-1 receptor antagonist.

Hepatocyte growth factor (HGF) prevents liver failure in various animal models including endotoxin-induced acute liver failure. We were interested to find out whether human HGF exerts anti-inflammatory effects by modulation of cytokine synthesis. Therefore, human HepG2 cells were cultured with increasing concentrations of HGF. HGF dose-dependently upregulated the production of interleukin-1 receptor antagonist (IL-1Ra). Incubation of HepG2 cells with interleukin-1beta (IL-1beta) caused an increase in IL-1Ra levels, while interleukin-6 (IL-6) had no effect on IL-1Ra synthesis. Co-stimulation of HepG2 cells with HGF + IL-1beta resulted in a synergistic effect on IL-1Ra mRNA and protein expression. Stimulation of freshly isolated mouse hepatocytes from male C57 BL/6 mice with HGF increased IL-1Ra mRNA and protein synthesis dose-dependently. A co-stimulation with HGF and IL-1beta had a synergistic effect on IL-1Ra mRNA expression but only a partially additive effect on IL-1Ra protein synthesis. HGF-induced IL-1Ra production was significantly decreased by the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Accordingly, HGF stimulation specifically increased MAPK-dependent signalling pathway (p42/44). In contrast, in preactivated PBMC mRNA expression and protein synthesis of IL-1Ra, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were unaffected after stimulation with HGF. In conclusion, our data suggest that HGF exerts anti-inflammatory effects by modulating the signal transduction cascade leading to increased expression of IL-1Ra, which might explain the protective and regenerative properties of this cytokine in animal models of liver failure.

Animals↗