Caveolin-1 Impacts on TGF-? Regulation of Metabolic Gene Signatures in Hepatocytes.

ABSTRACT: Caveolin-1 (CAV1) is a membrane protein associated with metabolism in various cell types. The transforming growth factor beta (TGF-?) is a pro-fibrogenic cytokine in the liver, but its metabolic gene signatures remain unclear to date. We have previously shown that CAV1 alters TGF-? signaling and blocks its pro-apoptotic function. Here, we defined TGF-?-induced metabolic gene signatures in hepatocytes and assessed whether CAV1 abundance affects TGF-? control of those metabolic genes. Microarray analyses of primary hepatocytes after TGF-? stimulation (48 h) showed differential expression of 4224 genes, of which 721 are metabolic genes (adjusted p < 0.001). Functional annotation analysis revealed that TGF-? mainly suppresses metabolic gene network, including genes involved in glutathione, cholesterol, fatty acid, and amino acid metabolism. TGF-? also upregulated several genes related to glycan metabolism and ion transport. In contrast to TGF-? effects, CAV1 knockdown triggered the upregulation of metabolic genes. Immortalized mouse hepatocytes (AML12 cells) were used to validate the gene changes induced by TGF-? stimulation and CAV1 knockdown. Noteworthy, of the TGF-? metabolic target genes, CAV1 modulated the expression of 228 (27%). In conclusion, we present several novel metabolic gene signatures of TGF-? in hepatocytes and show that CAV1 abundance alters almost a third of these genes. These findings could enable a better understanding of TGF-? function in normal and diseased liver especially where differential CAV1 level is implicated.

SUBMITTER: Han M 

PROVIDER: S-EPMC7005071 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature