Molecular characterization of mudskipper (Boleophthalmus pectinirostris) hypoxia-inducible factor-1α (HIF-1α) and analysis of its function in monocytes/macrophages

PLoS One. 2017 May 24;12(5):e0177960. doi: 10.1371/journal.pone.0177960. eCollection 2017.

Abstract

Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, very little information is available about the functions of HIF-1α in fish monocytes/macrophages (MO/MФ). In this study, the cDNA sequence of the mudskipper (Boleophthalmus pectinirostris) HIF-1α gene (BpHIF-1α) was determined. Sequence comparison and phylogenetic tree analysis showed that BpHIF-1α is clustered in the fish HIF-1α tree. Constitutive expression of BpHIF-1α mRNA was detected by real-time quantitative PCR in all tested tissues, and the expression was found to be dramatically increased in the skin, liver, spleen, and kidney after Edwardsiella tarda infection. In addition, hypoxia and infection induced the expression of the BpHIF-1α transcript and protein in MO/MФ, respectively. Hypoxia caused an increase in phagocytic and bactericidal capacity of mudskipper MO/MФ in a BpHIF-1α-dependent manner. BpHIF-1α induced an anti-inflammatory status in MO/MФ upon E. tarda infection and hypoxia. Therefore, BpHIF-1α may play a predominant role in the modulation of mudskipper MO/MФ function in the innate immune system.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Base Sequence
  • Cell Hypoxia / physiology
  • Cells, Cultured
  • Cloning, Molecular
  • Edwardsiella tarda / immunology*
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology
  • Fishes
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunity, Innate / immunology
  • Inflammation / immunology
  • Liver / metabolism
  • Macrophages / immunology*
  • Monocytes / immunology*
  • Phagocytosis / immunology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Skin / metabolism

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Small Interfering

Grants and funding

The project was supported by the Program for the National Natural Science Foundation of China (31472300) (http://www.nsfc.gov.cn/), Zhejiang Provincial Natural Science Foundation of China (LY17C190003) (http://www.zjnsf.gov.cn/), and Young Talent Cultivation Project of Zhejiang Association for Science and Technology (2016YCGC003) (http://www.zast.org.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.