TNF-α induces vascular endothelial cells apoptosis through overexpressing pregnancy induced noncoding RNA in Kawasaki disease model

Int J Biochem Cell Biol. 2016 Mar:72:118-124. doi: 10.1016/j.biocel.2016.01.011. Epub 2016 Jan 18.

Abstract

Kawasaki disease (KD) is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. The increased evidences showed that TNF-α was association with vascular inflammation in KD patients. However the detailed mechanism was still unclear. Recent studies indicated abnormal expressed long non-coding RNAs (LncRNAs) involved in many diseases. Thus the purpose of this study is to explore the role of lncRNAs in KD and find out the new target for KD treatment. In this study, firstly we verified the overexpressed TNF-α in KD patients, and found TNF-α was able to induce HUVECs apoptosis and inhibit HUVECs proliferation. After this we screened out pregnancy induced noncoding RNA (PINC) was significantly overexpression in TNF-α treated HUVECs. We also found PINC overexpressed in KD patients. For further study, we designed two siRNA of PINC. After silenced the expression of PINC in HUVECs, we found the Knockdown of PINC enhanced the viability of HUVECs treated with TNF-α, and increased the expression of anti-apoptotic and reduced the expression of apoptotic gene. These results suggest PINC involves in the process of TNF-α induces vascular endothelial cell apoptosis, it may become a new target for KD treatment.

Keywords: Apoptosis; Kawasaki disease; Long non-coding RNAs; Pregnancy induced noncoding RNA; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / drug effects
  • Cell Survival / drug effects
  • Female
  • Gene Expression Regulation* / drug effects
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Infant
  • Male
  • Mucocutaneous Lymph Node Syndrome / genetics
  • Mucocutaneous Lymph Node Syndrome / metabolism*
  • Mucocutaneous Lymph Node Syndrome / pathology*
  • RNA, Long Noncoding / genetics*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • RNA, Long Noncoding
  • Tumor Necrosis Factor-alpha