CircPTK2-miR-181c-5p-HMGB1: a new regulatory pathway for microglia activation and hippocampal neuronal apoptosis induced by sepsis

Li, Min; Hu, Jinwen; Peng, Yucong; Li, Jingbo; Ren, Reng

doi:10.1186/s10020-021-00305-3

Cited by 27 publications

(22 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The competitive endogenous RNA network of circRNAs, miRs, and mRNAs is pivotal for the pathogenesis, development, and severity of sepsis-induced cardiac damage [45]. Consistently, circPTK2 could act as the upstream gene of a competitive endogenous RNAs network to impact cellular survival, inflammatory reaction, and apoptosis in septic mice [35]. Therefore, we were encouraged to further explore the downstream mechanism of circPTK2 in sepsis.…”

Section: Discussionmentioning

confidence: 98%

“…Sepsis induces a series of abnormal variances in cell biological activities and thus causing myocardial damage [34]. As a member of the circRNA family, circPTK2 ablation contributes to cognitive function improvement, apoptosis and inflammation reduction, and prognosis promotion [35]. This experiment set out to find the functions of circPTK2 in the cardiac function of septic mice with the implication of the miR-29b-3p/BAK1 axis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1

Xi¹,

Fu²,

Li³

2021

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Objective: Sepsis is a predominant reason for the growing morbidity and mortality in the world. The role of circular RNAs (CircRNAs) is actively researched in sepsis. In this study, we attempt to find out the effect of CircRNA protein tyrosine kinase 2 (circPTK2) on cardiomyocyte apoptosis in septic mice. Methods: Septic mouse model was established by cecal ligation and puncture. Then circPTK2 expression was detected and the role of circPTK2 in myocardial damage was assessed after circPTK2 expression was silenced using Ad-sh-circHIPK3. The subcellular localization of circPTK2 was analyzed. Besides, the binding relation between circPTK2 and microRNA (miR)-29b-3p and between miR-29b-3p and BCL2 antagonist/killer 1 (BAK1) was verified. The expression of miR-29b-3p and BAK1 in the myocardium was detected. Functional rescue was conducted to evaluate the role of miR-29b-3p and BAK1 in cardiomyocyte apoptosis in septic mice. Results: CircPTK2 was highly expressed in the myocardium of septic mice, while circPTK2 silencing relieved the cardiac function and reduced inflammatory reaction and cardiomyocyte apoptosis of septic mice. Mechanically, circPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level. Inhibition of miR-29b-3p and BAK1 overexpression could counteract the protective role of circPTK2 silencing in the myocardium of septic mice. Conclusion: CircPTK2 is overexpressed in the myocardium of septic mice. CircPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level, to promote cardiomyocyte apoptosis, inflammatory response, and myocardial damage of the myocardium of septic mice.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1

Xi¹,

Fu²,

Li³

2021

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…As mentioned above, miR-181c-5p elevated the level of Bax/Bcl-2 ratio and cleaved-caspases 3, showed a pro-apoptotic effect in cardiomyocytes ( Ge et al, 2019 ). Nevertheless, miR-181c-5p acted on 3′-UTR region of HMGB1 mRNA and inhibited apoptosis in microglia ( Li et al, 2021 ). Compared with miR-181c-5p treatment, the overexpression of HMGB1 showed the adverse effect and enhanced apoptosis ( Li et al, 2021 ), confirming the anti-apoptotic role of miR-181c-5p.…”

Section: Mirnas Regulate Ddrmentioning

confidence: 99%

“…Nevertheless, miR-181c-5p acted on 3′-UTR region of HMGB1 mRNA and inhibited apoptosis in microglia ( Li et al, 2021 ). Compared with miR-181c-5p treatment, the overexpression of HMGB1 showed the adverse effect and enhanced apoptosis ( Li et al, 2021 ), confirming the anti-apoptotic role of miR-181c-5p. From the above, MAPKK /ERK, NF-κB, PI3K/AKT and Ras-associated factor-1/ERK 1/2 signaling pathways are all linked with the regulation of miR-7 on apoptosis.…”

Section: Mirnas Regulate Ddrmentioning

confidence: 99%

The Role of MicroRNA in DNA Damage Response

Tong

Liu

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

DNA is essential for the development and function of organisms. A number of factors affect DNA integrity and cause DNA damages, such as ultraviolet light, ionizing radiation and hydrogen peroxide. DNA damages activate a series of intracellular reactions, called DNA damage response, which play a crucial role in the pathogenesis of cancers and other diseases. MiRNA is a type of evolutionarily conserved non-coding RNA and affects the expression of target genes by post-transcriptional regulation. Increasing evidences suggested that the expression of some miRNAs was changed in tumor cases. MiRNAs may participate in DNA damage response and affect genomic stability via influencing the processes of cell cycle, DNA damage repair and apoptosis, thus ultimately impact on tumorigenesis. Therefore, the role of miRNA in DNA damage response is reviewed, to provide a theoretical basis for the mechanism of miRNAs’ effects on DNA damage response and for the research of new therapies for diseases.

show abstract

“…[ 17 ] Lipopolysaccharide (LPS) has been reported to promote the secretion of pro‐inflammatory cytokines and impair cognitive function during sepsis. [ 18 ] This study evaluates the potential effects of DEX treatment on preventing cognitive dysfunction and regulating pro‐inflammatory cytokines in POCD mice and LPS‐induced BV‐2 microglial cells together with HDAC2, HIF‐1α, and PFKFB3.…”

Section: Introductionmentioning

confidence: 99%

Effects of dexmedetomidine on cognitive dysfunction and neuroinflammation via the HDAC2/HIF‐1α/PFKFB3 axis in a murine model of postoperative cognitive dysfunction

Liu¹,

Zhang³

et al. 2022

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Inhibition of histone deacetylase (HDAC) may be a useful approach in the treatment of disorders characterized by cognitive dysfunction. Dexmedetomidine (DEX), an α2‐adrenoceptor (α2‐AR) agonist, has demonstrated neuroprotective effects. Here, we attempted to investigate the protective effects of DEX on postoperative cognitive dysfunction (POCD) involving HDAC2. Male C57BL/6 mice were selected to develop a POCD model, where HDAC2, HIF‐1α, and PFKFB3 expression was quantified. DEX was administered before POCD modeling. Then the cognitive function of POCD mice was evaluated with the open field and Y‐maze tests. Meanwhile, lipopolysaccharide (LPS) was employed to induce BV‐2 microglial cells to simulate the inflammatory response. The contents of TNF‐α, IL‐6, and IL‐10 were measured by enzyme‐linked immunosorbent assay (ELISA) in mouse serum and BV‐2 cell supernatant. Abundant expression of HDAC2, HIF‐1α, and PFKFB3 was confirmed in POCD mice (p < 0.05). Cognitive dysfunction in POCD mice could be alleviated following pharmacological inhibition of HDAC2 by FK228 (p < 0.05). Mechanistically, HDAC2 upregulated HIF‐1α and PFKFB3 and promoted the secretion of inflammatory factors in LPS‐exposed BV‐2 cells (p < 0.05). DEX attenuated neuroinflammation and the resulting cognitive dysfunction by decreasing HDAC2 expression and HIF‐1α‐dependent PFKFB3 upregulation in POCD mice (p < 0.05). In conclusion, DEX‐regulated HDAC2 may play an inhibitory role in mice with POCD through regulation of the HIF‐1α/PFKFB3 axis.

show abstract

CircPTK2-miR-181c-5p-HMGB1: a new regulatory pathway for microglia activation and hippocampal neuronal apoptosis induced by sepsis

Cited by 27 publications

References 38 publications

CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1

CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1

The Role of MicroRNA in DNA Damage Response

Effects of dexmedetomidine on cognitive dysfunction and neuroinflammation via the HDAC2/HIF‐1α/PFKFB3 axis in a murine model of postoperative cognitive dysfunction

Contact Info

Product

Resources

About