Hepatic PTPRD expression is associated with signalling pathways regulating glucose and lipid metabolism. (IMAGE)
Caption
(a) GSEA showing significantly enriched (false discovery rate (FDR) <0.05) signalling pathways associated with low hepatic PTPRD expression in humans without CLD (n=38, GSE61260). (b) Ptprd-deficient mouse model presents a 200 bp deletion in the genomic region coding for the first phosphatase domain of PTPRD. Genotyping by PCR of liver samples from Ptprd+/+ mice (n=3) compared with Ptprd−/− animals (n=3). (c) Genomic deletion of Ptprd induces a significant (U-test) downregulation of its expression at the mRNA level when comparing Ptprd+/+ (n=6), Ptprd+/− (n=4) and Ptprd−/− (n=5) mice, as assessed by RT-qPCR. Data are presented as means±SD. (d) PTPRD protein level is impaired in Ptprd-deficient mice, as shown in liver samples analysed by western blot. (e) Ptprd+/− mice exhibit a pro-diabetic transcriptional pattern in the liver microenvironment. GSEA of liver expression data from Ptprd+/− mice (n=3) as compared with Ptprd+/+ animals (n=3), showing a significant upregulation of the Reactome diabetes pathways gene set and a downregulation of the Kegg insulin signalling pathway (FDR <0.05). AMPK, AMP-activated protein kinase; CLD, chronic liver disease; FN, fibronectin; GSEA, gene set enrichment analysis; IFN, interferon; IL, interleukin; mTOR, mechanistic target of rapamycin kinase; NES, normalised enrichment score; NF-κB, nuclear factor kappa B; PKB, protein kinase B; PPARα, peroxisome proliferator-activated receptor alpha; PTPRD, protein tyrosine phosphatase delta; STAT, signal transducer and activator of transcription; TNFα, tumour necrosis factor alpha. *P<0.05, ****p<0.0001.
Credit
By Armando Andres Roca Suarez, Frank Jühling, Julien Moehlin et al.
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