Caveolin-1 (CAV1) is a membrane protein associated to metabolism in quite a few cell types. The remodeling progress subject beta (TGF-β) is a pro-fibrogenic cytokine in the liver, nonetheless its metabolic gene signatures keep unclear so far. We have beforehand confirmed that CAV1 alters TGF-β signaling and blocks its pro-apoptotic function.
Here, we outlined TGF-β-induced metabolic gene signatures in hepatocytes and assessed whether or not or not CAV1 abundance impacts TGF-β administration of these metabolic genes.
Microarray analyses of fundamental hepatocytes after TGF-β stimulation (48 h) confirmed differential expression of 4224 genes, of which 721 are metabolic genes (adjusted p < 0.001). Functional annotation analysis revealed that TGF-β primarily suppresses metabolic gene neighborhood, along with genes involved in glutathione, ldl ldl cholesterol, fatty acid, and amino acid metabolism. TGF-β moreover upregulated a quantity of genes related to glycan metabolism and ion transport.
In distinction to TGF-β outcomes, CAV1 knockdown triggered the upregulation of metabolic genes. Immortalized mouse hepatocytes (AML12 cells) had been used to validate the gene modifications induced by TGF-β stimulation and CAV1 knockdown. Noteworthy, of the TGF-β metabolic aim genes, CAV1 modulated the expression of 228 (27%). In conclusion, we present a quantity of novel metabolic gene signatures of TGF-β in hepatocytes and current that CAV1 abundance alters almost a third of these genes.
These findings could enable a larger understanding of TGF-β function in common and diseased liver notably the place differential CAV1 stage is implicated.
Hepatocyte caveolin-1 modulates metabolic gene profiles and capabilities in non-alcoholic fatty liver sickness.
Caveolin-1 (CAV1) is an important regulator of lipid accumulation and metabolism. Previous analysis have confirmed that worldwide Cav1 deficiency impacts lipid metabolism and hepatic steatosis.
We aimed to analysis the outcomes of hepatocyte-specific Cav1 knockout under healthful circumstances and upon non-alcoholic fatty liver sickness (NAFLD) progress. Male and female hepatocyte-specific Cav1 knockout (HepCAV1ko) mice had been fed a methionine/choline (MCD) poor meals routine for 4 weeks. MCD feeding induced excessive hepatic steatosis and slight fibrosis.
In addition, liver function parameters, i.e., ALT, AST, and GLDH, had been elevated, whereas ldl ldl cholesterol and glucose stage had been diminished upon MCD feeding. These variations weren’t affected by hepatocyte-specific Cav1 knockout.
Microarray analysis confirmed sturdy variations in gene expression profiles of livers from HepCAV1ko mice in distinction these of worldwide Cav1 knockout animals. Pathway enrichment analysis acknowledged that metabolic alterations had been sex-dimorphically regulated by hepatocyte-specific CAV1. In male HepCAV1ko mice, metabolic pathways had been suppressed in NAFLD, whereas in female knockout mice induced.
Moreover, gender-specific transcription profiles had been modulated in healthful animals. In conclusion, our outcomes exhibit that hepatocyte-specific Cav1 knockout significantly altered gene profiles, did not have an impact on liver steatosis and fibrosis in NAFLD and that gender had excessive affect on gene expression patterns in healthful and diseased hepatocyte-specific Cav1 knockout mice.