Effects and Mechanism of lncRNA CRNDE on Sepsis-Induced Acute Kidney Injury

Abstract

Objective. To investigate the effects of lncRNA CRNDE on sepsis-associated acute kidney injury in the human kidney 2 cell line and explore the potential mechanisms. Methods. HK-2 cells were treated with lipopolysaccharides to induce injuries. The expression of CRNDE and miR-146a in HK-2 cells were altered by a transient transfection assay. Cell apoptosis was detected by a flow cytometry assay, and the levels of inflammatory cytokines including TNF-α, IL-6, IL-8, and IL-1β were assessed by ELISA. Furthermore, western blot analysis was performed to detect the expression levels of TLR4/NF-κB pathway-related proteins. And a luciferase reporter gene assay was used to verify if miR-146a was the target of CRNDE. Results. LPS treatment increased CRNDE expression in HK-2 cells. CRNDE overexpression enhanced cell injuries in HK-2 cells significantly increasing inflammatory cytokine levels, including TNF-α, IL-6, IL-8, and IL-1β, and cell apoptosis. In addition, CRNDE overexpression further activated the TLR4/NF-κB pathways in HK-2 cells. Inversely, opposite results were observed in the miR-146a mimic treatment group, and the miR-146a inhibitor could reverse the protein expression changes of TLR4/NF-κB in the si-CRNDE and LPS treatment group. Conclusion. This study demonstrated that CRNDE overexpression could activate the TLR4/NF-κB signaling pathway by regulating miR-146a, which accelerated LPS-induced inflammation and apoptosis in HK-2 cells.

Long Non-Coding RNAs as Biomarkers and Therapeutic Targets in Sepsis

“…CRNDE was reported to be protective of myocardial and liver injury during sepsis (57,58). The overexpression of CRNDE was reported to accelerate LPS-induced inflammatory response in kidney by activating TLR4/NF-kB signaling pathway (59). These results reflected the study of Sun et al (1992) (60) who also found that inhibiting CRNDE could alleviate sepsis-induced kidney injury by blocking the activation of TLR3/NF-kB signaling.…”

“…CRNDE was reported to be protective of myocardial and liver injury during sepsis ( 57 , 58 ). The overexpression of CRNDE was reported to accelerate LPS-induced inflammatory response in kidney by activating TLR4/NF-κB signaling pathway ( 59 ). These results reflected the study of Sun et al.…”

Long non‐coding RNA colorectal neoplasia differentially expressed correlates negatively with miR‐33a and miR‐495 and positively with inflammatory cytokines in asthmatic children

“…Therefore, we performed this study and discovered that lncRNA CRNDE was positively correlated with inflammatory cytokines and exacerbation severity in paediatric patients with asthma. The possible reasons to explain these were as follows: (a) LncRNA CRNDE might activate serval signalling pathways (such as NF‐ κ B and JAK–STAT signalling pathways) to promote the production of inflammatory cytokines, thereby resulted in higher asthmatic risk 6,7 . (b) As mentioned earlier, lncRNA CRNDE was positively correlated with increased inflammatory cytokines production, thereby led to impaired immune response and further resulted in increased chance of viral respiratory infection to develop exacerbation in paediatric patients with asthma 4 .…”

“…Long non‐coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) located on human chromosome 16, is highly involved in cancer biology, which has been reported to be involved in promotion of cell proliferation, inhibition of cell apoptosis and assistance of epithelial‐to‐mesenchymal transition 5 . Regarding its role in inflammation diseases, overexpression of lncRNA CRNDE activates toll‐like receptor (TLR)‐4/nuclear factor (NF)‐ κ B pathway and further leads to production of inflammatory cytokines (such as tumour necrosis factor (TNF)‐ α , interleukin (IL)‐1 β and IL‐6) in lipopolysaccharide (LPS) treated HK‐2 cells 6 . Meanwhile, upregulated lncRNA CRNDE promotes inflammatory cytokines production through the activation of NF‐ κ B and Janus kinase/signal transduction and activator of transcription (JAK–STAT) signalling pathways in LPS treated WI‐38 cells 7 .…”

Non-Coding RNAs in Kidney Diseases: The Long and Short of Them

“…CRNDE was upregulated in LPS injected mice and its inhibition improved renal function by regulating the TLR3/NF-κB pathway [ 36 ]. Similarly, another study demonstrated that CRNDE overexpression activated TLR4/NF-κB pathway via miR-146a, increasing inflammation and cell death in HK-2 cells treated with LPS [ 37 ].…”