The role of circ_0001126 in Hcy-induced ferroptosis of MPC-5 cells
WANG Ziqing
DING Ning
YANG Lianpeng
WANG Linyun
LI Jingrui
WANG Yibin
LI Guizhong
JIANG Yideng
LU Guanjun
Abstract：Objective To explore the role of circ_0001126 in homocysteine(Hcy)-induced ferroptosis of Mouse Podocyte Cell line-5(MPC-5)cells.Methods MPC-5 cells were cultured in vitro and divided into a control group(0 µmol/L Hcy)and an Hcy group(80 µmol/L Hcy).After 48 hours of cell intervention,the expressions of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)proteins were detected by Western blot.The levels of malondialdehyde(MDA)and glutathione(GSH)were measured using a kit,and the level of Fe²⁺ was observed using a fluorescence assay kit.High-throughput sequencing was employed to screen specific circular RNA(circRNA)in podocytes from the control group and the Hcy group,and quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used for validation.Bioinformatics was used to predict chromosome location and conservation.After transfection with si-circ_0001126 and its negative control(si-NC),the expressions of GPX4 and SLC7A11 proteins and their mRNAs were detected by Western blot and qRT-PCR,respectively.The intracellular MDA level was measured by a malondialdehyde assay kit,the intracellular GSH level was measured by a GSH assay kit,and the intracellular Fe²⁺ level was observed by a fluorescence assay kit.Results Compared with the Control group,the Hcy group exhibited a significant decrease in the expression of ferroptosis related proteins GPX4 and SLC7A11(P<0.001),a notable increase in the expression levels of Fe2+and MDA(P<0.001),and a marked decrease in GSH levels(P<0.001);High throughput sequencing revealed a total of 12 circRNAs with differential expression in the Hcy group,including 8 up-regulated and 4 down-regulated.Based on|log2foldchange|(≥2)and P value(P<0.05),circ_0001126 was screened out,and qRT-PCR was used to verify its upregulation in the Hcy group,which is consistent with the sequencing results(P<0.001).Analysis using the UCSC Genome Browser Gateway and circbase showed that circ_0001126 is primarily located at chr3:51659420-51660998,formed by the cyclization of the second exon of the Maml3 gene and is highly conserved.Transfection of si-circRNAs demonstrated that si-circ_0001126-309 had the optimal interference efficiency(P<0.001).Compared with the Hcy+si-NC group,the Hcy+si-circ_0001126 group showed a significant increase in the expression of ferroptosis-related proteins GPX4 and SLC7A11(P<0.001),a notable decrease in Fe2+and MDA expression levels(P<0.001),and an marked increase in GSH levels(P<0.001).Conclusion circ_0001126 shows a significant up-regulation in MPC-5 cells treated with Hcy,and down-regulating its expression can inhibit Hcy-induced ferroptosis in MPC-5 cells.
Keywords：circ_0001126homocysteinechronic kidney diseasepodocytesferroptosis
Publication Date：2026-01-25
Online Publishing Date：2026-01-28(First online date of this platform, not the publication date of the document)
Pages：11( 201-211 )