Mechanism of LINC00963 in alleviating myocardial injury in sepsis through regulating the TLR4/NF-κB pathway

YANG Hu; GUO Xia; QIAO Shunyi; JIA Lin; SUN Xiaotong; LI Dongkun.

PDF(1303 KB)

Medical Journal of the Chinese People Armed Police Forces ›› 2025, Vol. 36 ›› Issue (11) : 965-969.

ORIGINAL ARTICLES

Mechanism of LINC00963 in alleviating myocardial injury in sepsis through regulating the TLR4/NF-κB pathway

YANG Hu¹, GUO Xia², QIAO Shunyi¹, JIA Lin³, SUN Xiaotong¹, LI Dongkun¹.

Author information +

History +

Abstract

Objective To explore the mechanism of long non-coding RNA LINC00963 in alleviating myocardial injury in sepsis through regulating the TLR4/MyD88/NF-κB signaling pathway. Methods A murine sepsis model was established by cecal ligation and puncture (CLP) (n=24). Mice were randomly divided into a LINC00963 overexpression lentivirus group (LV-LINC00963-OE), a LINC00963 knockdown lentivirus group (LV-LINC00963-KD), and a corresponding negative control group. RAW264.7 macrophages were transfected with lentiviral vectors, and the LINC00963 expression was regulated by tail vein injection. Cardiac tissues were harvested 7 days after surgery for HE staining to evaluate the degree of pathological injury; Western blot was used to detect the expression of TNF-α, NF-κB p65, MyD88, and AP-1 proteins. Results The myocardial interstitial edema score in the LV-LINC00963-KD group was significantly higher than that in the control group [(3.8±0.4) vs. (1.2±0.3), P<0.01], and the expression of pro-inflammatory factors TNF-α, NF-κB p65, MyD88, and AP-1 was upregulated by 1.8 to 2.5 times, with statistically significant differences (P<0.01). Conversely, in the LV-LINC00963-OE group, the above indicators were significantly reduced , with statistically significant differences (P<0.01). Conclusions LINC00963 mediates the inflammatory response by targeting the TLR4/MyD88/NF-κB signaling pathway, alleviating myocardial injury in sepsis, providing a potential therapeutic target for clinical intervention of septic cardiomyopathy.

Key words

septic cardiomyopathy / LINC00963 / pro-inflammatory cytokines / TLR4/MyD88/NF-κB signaling pathway / apoptosis

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

YANG Hu, GUO Xia, QIAO Shunyi, JIA Lin, SUN Xiaotong, LI Dongkun.. Mechanism of LINC00963 in alleviating myocardial injury in sepsis through regulating the TLR4/NF-κB pathway[J]. Medical Journal of the Chinese People Armed Police Forces. 2025, 36(11): 965-969

References

[1] Singer M, Deutschman C S, Seymour C W, et al. The third international consensus definitions for sepsis and septic shock(Sepsis-3)[J]. JAMA, 2016, 315(8):801-810.
[2] Wang X, Liu Q, Zhu H, et al. Mitochondrial dysfunction in septic cardiomyopathy: mechanisms and therapeutic strategies[J]. J Mol Cell Cardiol, 2021, 154:34-45.
[3] 张涛,刘红梅,陈志强,等. 长链非编码RNA LINC00963在脓毒症心肌损伤患者血清中的表达及临床意义[J].中华危重病急救医学, 2023, 35(7): 721-726.
[4] Chen L L, Zhao Y, Wang M, et al. Emerging roles of long non-coding RNAs in sepsis-induced organ injury[J]. Front Immunol, 2022, 13:903812.
[5] Rittirsch D, Huber-Lang M S, Flierl M A, et al. Immunodesign of experimental sepsis by cecal ligation and puncture[J]. Nat Protoc,2009,4(1):31-36.
[6] Suzuki K, Ota H, Sasagawa S, et al. Assay method for myeloperoxidase in human polymorphonuclear leukocytes[J]. Anal Biochem,1983,132(2):345-352.
[7] Zhang H, Li Y, Wang J, et al. LncRNA MALAT1 attenuates sepsis-induced myocardial injury via miR-150-5p/PDCD4 axis[J]. Shock, 2022, 57(2):267-275.
[8] Wang Y, Chen L, Zhang Q, et al. LINC00963 exacerbates TNF-α-mediated mitochondrial dysfunction in septic cardiomyopathy[J]. J Mol Cell Biol, 2023, 15(2):123-135.
[9] Fu Y J, Zhang K, Liu H, et al. TLR4/MyD88/NF-κB signaling in sepsis-induced cardiomyopathy[J]. J Am Heart Assoc, 2020, 9(9):e016551.
[10] 王建军, 李伟, 张涛, 等. 脓毒症心肌损伤中TLR4信号通路的调控机制[J]. 武警医学, 2021, 32(5):401-405.
[11] Zhang H, Wu T, Li X, et al. LncRNA MALT4 inhibits TLR4/NF-κB signaling by sponging miR-155-5p in septic myocardial injury[J]. Nat Commun, 2023, 14:5123.
[12] Wang L, Zhao M, Chen X, et al. LncRNA HOTAIR exacerbates myocardial inflammation via the TLR4/MyD88/NF-κB axis in sepsis[J]. Circ Res, 2023, 133(1):45-58.
[13] Tan S, Chen Z, Liu Y, et al. LncRNA-mediated epigenetic silencing of NF-κB inhibitors exacerbates septic cardiomyopathy[J]. Circ Res, 2023, 132(5):45-60.
[14] Li R, Wang J, Zhang L, et al. LncRNA H19 suppresses JNK/AP-1 signaling to alleviate myocardial ischemia-reperfusion injury[J]. Cardiovasc Res, 2021, 117(12):2457-2470.
[15] 陈立, 吴芳, 郑伟, 等. LncRNA HOTAIR通过miR-146a/TRAF6轴调控巨噬细胞炎症反应加重脓毒症心肌损伤的机制[J]. 中国病理生理杂志, 2022, 38(11): 1985-1992.
[16] Liu Y, Zhang M, Wang S, et al. LncRNA NEAT1 regulates NLRP3 inflammasome activation via MyD88 ubiquitination in septic cardiomyopathy[J]. J Mol Cell Cardiol, 2023, 174:45-58.
[17] Wang J, Xu H, Li F, et al. AP-1 as a dual regulator of inflammation and fibrosis in cardiovascular diseases[J]. Pharmacol Ther, 2022, 233:108025.
[18] Luo Y, Wang X, Chen J, et al. LncRNA NEAT1 promotes NLRP3 inflammasome activation via m6A modification in septic cardiomyopathy[J]. Nat Commun, 2023, 14:4321-4331.
[19] Chen Z, Li H, Wu Y, et al. LncRNA MEG3 suppresses NLRP3 inflammasome via HDAC2-dependent chromatin remodeling in sepsis[J]. Circ Res, 2023, 132:987-1002.
[20] Li R, Zhang H, Chen M, et al. LncRNA H19 attenuates cardiac fibrosis by targeting the JNK/AP-1 pathway in sepsis[J]. Nat Commun, 2023, 14:6890-6899.
[21] Liu Y, Zhao X, Zhang W, et al. LncRNA Kcnq1ot1 modulates macrophage polarization via miR-214-3p/DUSP1 axis in septic cardiomyopathy[J]. Nat Commun, 2023, 14:4321-4325.
[22] Zhou M T, Zhang Q, Li S, et al. Targeting AP-1/NF-κB heterodimerization: a novel anti-inflammatory strategy in septic cardiomyopathy[J]. J Clin Invest, 2024, 134(3):e178921.
[23] Andersson U, Ottosson L, Palmblad K, et al. Extracellular HMGB1 amplifies macrophage-cardiomyocyte crosstalk in sepsis via RAGE/TLR4[J]. Intensive Care Med, 2023, 49(11):1293-1305.
[24] Zhang Y, Wang L, Chen H, et al. LncRNA TUG1 coordinates NF-κB and Nrf2 pathways to mitigate oxidative stress in sepsis[J]. Circ Res, 2023, 132:145-160.
[25] Tan S, Liu F, Wang H, et al. LncRNA-mediated DNA methylation suppresses PPARγ signaling in septic myocardial injury[J]. Nat Commun, 2023, 14:8902-8906.