WISP1 mediates hepatic warm ischemia reperfusion injury via TLR4 signaling in mice

Sci Rep. 2016 Jan 29:6:20141. doi: 10.1038/srep20141.

Abstract

Wnt-induced secreted protein-1 (WISP1) is an extracellular matrix protein that has been reported in cancer researches. Our previous studies on WISP1 implied it could be a harmful mediator in septic mice. However, its role in liver ischemia reperfusion (I/R) injury is unknown. This study investigated the effects of WISP1 on liver I/R damage. Male C57BL/6 wild-type mice were used to undergo 60 min segmental (70%) ischemia. WISP1 expression was measured after indicated time points of reperfusion. Anti-WISP1 antibody was injected intraperitoneally to mice. Toll-like receptor 4 (TLR4) knockout mice and TIR-domain-containing adaptor inducing interferon-β (TRIF) knockout mice were adopted in this study. WISP1 was significantly enhanced after 6 h of reperfusion when compared with sham treated mice and significantly decreased either by TLR4 knockout mice or TRIF knockout mice. Anti-WISP1 antibody significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological changes and pro-inflammatory cytokine levels in the mice following I/R. Furthermore, significantly increased serum transaminase levels were found in C57 wild-type mice treated with recombinant WISP1 protein, but not found in TLR4 knockout or TRIF knockout mice subjected to liver I/R. Taken together, WISP1 might contribute to hepatic ischemia reperfusion injury in mice and possibly depends on TLR4/TRIF signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • CCN Intercellular Signaling Proteins / biosynthesis*
  • CCN Intercellular Signaling Proteins / genetics
  • Gene Expression Regulation*
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Signal Transduction*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Adaptor Proteins, Vesicular Transport
  • CCN Intercellular Signaling Proteins
  • CCN4 protein, mouse
  • Proto-Oncogene Proteins
  • TICAM-1 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4