Hepatocyte nuclear factors as possible C-reactive protein transcriptional inducer in the liver and white adipose tissue of rats with experimental chronic renal failure

Mol Cell Biochem. 2018 Sep;446(1-2):11-23. doi: 10.1007/s11010-018-3268-1. Epub 2018 Jan 12.

Abstract

Inflammation related to chronic kidney disease (CKD) is an important clinical problem. We recently determined that hepatocyte nuclear factor 1α (HNF1α) was upregulated in the livers of chronic renal failure (CRF) rats-experimental model of CKD. Considering that the promoter region of gene encoding C-reactive protein (CRP) contains binding sites for HNF1α and that the loss-of-function mutation in the Hnfs1α leads to significant reduction in circulating CRP levels, we hypothesized that HNF1α can activate the Crp in CRF rats. Here, we found coordinated upregulation of genes encoding CRP, interleukin-6 (IL-6), HNF1α, and HNF4α in the livers and white adipose tissue (WAT) of CRF rats, as compared to the pair-fed and control animals. This was accompanied by elevated serum levels of CRP and IL-6. CRP and HNFs' mRNA levels correlated positively with CRP and HNFs' protein levels in the liver and WAT. Similar upregulation of the Crp, Il-6, and Hnfs in the liver and WAT and increased serum CRP and IL-6 concentrations were found in lipopolysaccharide (LPS)-induced systemic inflammation in rats. Moreover, silencing HNF1α in HepG2 cells by small interfering RNA led to decrease in CRP mRNA levels. Our results suggests that (a) HNFs act in concert with IL-6 in the upregulation of CRP production by the liver and WAT, leading to an increase in circulating CRP concentration in CRF rats and (b) CRF-related inflammation plays an important role in the upregulation of genes that encode HNFs and CRP in the liver and WAT of CRF rats.

Keywords: CRF; CRP; HNF1; HNF4; Il-6; LPS.

MeSH terms

  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Animals
  • C-Reactive Protein / biosynthesis*
  • C-Reactive Protein / genetics
  • Disease Models, Animal
  • Hep G2 Cells
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism*
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / pathology
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Rats
  • Rats, Wistar
  • Transcription, Genetic*
  • Up-Regulation*

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • Hnf1a protein, rat
  • Hnf4a protein, rat
  • Interleukin-6
  • C-Reactive Protein