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

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.

LncRNAs Stand as Potent Biomarkers and Therapeutic Targets for Stroke

“…Moreover, in type VII collagenase-induced intracerebral hemorrhage rats, silencing of lncRNA NKILA decreased neurological deficits, exacerbated hematoma and brain edema, and induced BBB breakdown, further leading to hippocampal neuron loss and inflammation cytokines production. The endoplasmic reticulum stress (ERS)/autophagy pathway and NF-κB signaling pathway were involved in this process (Jia et al, 2018). Dong et al (2018) found that lncRNA FENDRR regulated the vascular endothelial growth factor A (VEGFA)/miR-126 axis and contributed to the apoptosis of BMECs in hypertensive intracerebral hemorrhage mice models.…”

Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice

“…Long non-coding RNAs (lncRNAs) is a subtype of non-coding RNAs with the transcripts of more than 200 nucleotides [11]. Although lncRNAs have no protein-coding capacity, they may regulate physiological functions as well as pathological processes in many diseases [12][13][14][15]. In particular, the activation of lncRNAs might regulate the expression of proteincoding genes through sophisticated mechanisms in ocular disorders [16][17][18][19].…”

Involvement of lncRNAs and Macrophages: Potential Regulatory Link to Angiogenesis

“…Long noncoding RNAs (lncRNAs) are those which demonstrate no apparent protein-coding capacity and longer than 200 nucleotides [10]. Recent studies indicated a variety of regulatory functions of lncRNAs in a wide range of cellular and developmental processes as well as pathogenesis [11][12][13][14][15].…”