Effect of lncRNA CRNDE on Macrophage Pyroptosis and M1-type Polarization in Ulcerative Colitis Mice via ERK1/2 Pathway

doi:10.3870/j.issn.1672-8009.2026.01.005

Abstract

Abstract: Objective To investigate the effect of long non-coding RNA(lncRNA)CRNDE on macrophage pyroptosis and M1 polarization in ulcerative colitis(UC)mice and the potential mechanism. Methods The UC mouse model was established,and colon length,disease activity index(DAI)were measured to validate the model.RAW264.7 cells were divided into 4 groups:Ctrl group,pcDNA-null group,pcDNA-CRNDE group,and pcDNA-CRNDE+LY3214996 group.The expression levels of lncRNA CRNDE,cleaved-Caspase-1,cleaved-GSDMD,ERK1/2,and phosphorylated ERK1/2(p-ERK1/2)were detected by qRT-PCR or Western blotting.The proportion of F4/80⁺CD86⁺macrophages was measured by flow cytometry. Results In the model group,the DAI score was increased,the colon length was shortened,and the expression levels of lncRNA CRNDE,cleaved-Caspase-1,cleaved-GSDMD,and p-ERK1/2 were upregulated,and the proportion of F4/80⁺CD86⁺ macrophages was increased(all P<0.05).In RAW264.7 cells,lncRNA CRNDE and cleaved-Caspase-1、cleaved-GSDMD、p-ERK1/2 expression in the pcDNA-CRNDE group was upregulated when compared with that in the pcDNA-null group,and that was downregulated after LY3214996 treatment(all P<0.05). Conclusion lncRNA CRNDE promotes macrophage pyroptosis and M1 polarization in UC mice by activating the ERK1/2 pathway,suggesting it may be a potential therapeutic target for UC.

Key words: ulcerative colitis, lncRNA CRNDE, macrophage, pyroptosis, M1 polarization

CLC Number:

R342.3

Feiluore Dilixiati, Zulihumaer Alimujiang, DU Jinxuan. Effect of lncRNA CRNDE on Macrophage Pyroptosis and M1-type Polarization in Ulcerative Colitis Mice via ERK1/2 Pathway[J]. Journal of Medical Molecular Biology, 2026, 23(1): 36-42.

References

[1] SEGAL J P,LEBLANC J F,HART A L.Ulcerative colitis:an update[J].Clin Med,2021,21(2):135-139.
[2] PORTER R J,KALLA R,HO G T.Ulcerative colitis:recent advances in the understanding of disease pathogenesis[J].F1000 Res,2020,9:294.
[3] FENTON C G,RAY M K,MENG W,et al.Methylation-regulated long non-coding RNA expression in ulcerative colitis[J].Int J Mol Sci,2023,24(13):10500.
[4] TIAN C,GAO J,YANG L,et al.Non-coding RNA regulation of macrophage function in asthma[J].Cell Signal,2023,112:110926.
[5] CHINI A,GUHA P,MALLADI V S,et al.Novel long non-coding RNAs associated with inflammation and macrophage activation in human[J].Sci Rep,2023,13(1):4036.
[6] DING N,LUO H,PENG T,et al.Bioinformatics analysis on differentially expressed genes between colorectal adenoma and colorectal adenocarcinoma[J].Scot Med J,2022,67(4):178-188.
[7] TANG D,ZHAO L,MU R,et al.LncRNA colorectal neoplasia differentially expressed promotes glycolysis of liver cancer cells by regulating hypoxia-inducible factor 1α[J].Chin J Physiol,2022,65(6):311-318.
[8] ZHANG Q,ZHU D,LI Q.LncRNA CRNDE exacerbates neuropathic pain in chronic constriction injury-induced(CCI)rats through regulating miR-146a-5p/WNT5A pathway[J].Bioengineered,2021,12(1):7348-7359.
[9] YANG F,LI X F,CHENG L N,et al.Long non-coding RNA CRNDE promotes cell apoptosis by suppressing miR-495 in inflammatory bowel disease[J].Exp Cell Res,2019,382(2):111484.
[10] KAZEMIFARD N,FARMANI M,BARADARAN GHAVAMI S,et al.A prediction of the CRNDE role by modulating NF-κB pathway in inflammatory bowel disease(IBD)[J].Biochem Biophys Rep,2024,38:101731.
[11] YIN L,YAN J,CHEN W.Mechanism of lncRNA-H19 inintestinal injury of mice with ulcerative colitis[J].Int Arch Allergy Immunol,2022,183(9):985-996.
[12] CAO L,TAN Q,ZHU R,et al.LncRNA MIR4435-2 HG suppression regulates macrophage M1/M2 polarization and reduces intestinal inflammation in mice with ulcerative colitis[J].Cytokine,2023,170:156338.
[13] YUAN Y,HE Y,WASTI B,et al.lncRNA CRNDE affects Th17/IL-17 A and inhibits epithelial-mesenchymal transition in lung epithelial cells reducing asthma signs[J].Oxid Med Cell Longev,2023,2023:2092184.
[14] HEYDARI R,FAYAZZADEH S,SHAHROKH S,et al.Plasma extracellular vesicle LncRNA H19 as a potential diagnostic biomarker for inflammatory bowel diseases[J].Inflamm Bowel Dis,2024,30(5):795-807.
[15] DAI Y,LU Q,LI P,et al.Xianglian Pill attenuates ulcerative colitis through TLR4/MyD88/NF-κB signaling pathway[J].J Ethnopharmacol,2023,300:115690.
[16] ZHUANG H,LV Q,ZHONG C,et al.Tilirosideameliorates ulcerative colitis by restoring the M1/M2 macrophage balance via the HIF-1α/glycolysis pathway[J].Front Immunol,2021,12:649463.
[17] LIANG L,LIU L,ZHOU W,et al.Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/WNT/ERK signaling pathway[J].Clin Sci,2022,136(4):291-307.