Long noncoding ribonucleic acid NKILA induces the endoplasmic reticulum stress/autophagy pathway and inhibits the nuclear factor-k-gene binding pathway in rats after intracerebral hemorrhage

J Cell Physiol. 2018 Nov;233(11):8839-8849. doi: 10.1002/jcp.26798. Epub 2018 Jun 12.

Abstract

Long noncoding RNAs (lncRNAs) have emerged as an important class of molecules that have been associated with brain function and neurological disease, but the expression profiles of lncRNAs after intracerebral hemorrhage (ICH) remain to be elucidated. In this study, we determined the expression pattern of nuclear factor-k-gene binding (NF-kB) interacting lncRNA (NKILA) after ICH and examined its respective effects on the endoplasmic reticulum stress (ERS)/autophagy pathway, hippocampal neuron loss, and the NF-kB pathway after type VII collagenase-induced ICH in rats. The regulatory mechanisms of NKILA were investigated by an intraperitoneal injection of small interfering (siRNA) against NKILA into rats after ICH. NKILA inhibition mediated by siRNA against NKILA was shown to significantly reduce ERS and autophagy, activate the NF-kB pathway, decrease neurological deficits, brain edema, and injury, and induce blood-brain barrier breakdown, further leading to hippocampal neuron loss and the production of inflammation cytokines. Taken together, the demonstration that NKILA induces the ERS/autophagy pathway and inhibits the NF-kB pathway after ICH supports the concept that NKILA functions as a novel target that is required for the attenuation of brain injuries after ICH.

Keywords: NF-κB interacting lncRNA (NKILA); NF-κB signaling pathway; autophagy; endoplasmic reticulum stress (ERS); intracerebral hemorrhage (ICH).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics
  • Brain / metabolism
  • Brain / pathology
  • Brain Injuries / genetics
  • Brain Injuries / pathology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / pathology
  • Endoplasmic Reticulum Stress / genetics*
  • Gene Expression Regulation
  • Humans
  • Male
  • NF-kappa B / genetics
  • Neurons / pathology*
  • Protein Binding
  • RNA, Long Noncoding / genetics*
  • Rats
  • Signal Transduction / genetics

Substances

  • NF-kappa B
  • RNA, Long Noncoding