circRNA-007371 Regulates CX3CR1 to Mediate Hepatic Stellate Cell Pyroptosis in Liver Fibrosis

doi:10.3870/j.issn.1672-0741.25.09.021

Abstract

Abstract: Objective To investigate the role of circRNA-007371 in regulating CX3CR1-mediated hepatic stellate cell(HSC)pyroptosis in liver fibrosis(LF)and its possible mechanism. Methods Thirty rats were divided into control group,LF group and low expression circRNA-007371 group,with 10 rats in each group.HSC-T6 cells were cultured and divided into control group,circRNA-007371 overexpression group and NLRP3 inhibition(Antcin A)group.The level of LF was detected by Sirius Red staining.The levels of α-SMA and Collagen1 proteins in liver tissue were detected by immunofluorescence staining.The mRNA levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in liver tissue and HSC-T6 were detected by qRT-PCR.HE staining was used to detect the pathological changes of liver tissue.Masson staining was used to detect collagen deposition in liver tissue.Western blotting was used to detect NLRP3,Caspase-1 and GSDMD protein levels in liver tissue and HSC-T6.The IL-1β and IL-18 levels in serum and HSC-T6 were detected by ELISA. Results Compared with the control group,the liver tissue of LF group showed hyperplasia of collagen fiber,the protein expression levels of α-SMA and Collagen1,the mRNA expression levels of circRNA-007371 and CX3CR1 were increased(P<0.05),the liver tissue showed pathological injury,accompanied by liver steatosis and fat cavity;hepatic lobular structure was abnormal,collagen was increased significantly,the levels of NLRP3,Caspase-1 and GSDMD proteins in liver tissue were increased(P<0.05),and the serum IL-1β and IL-18 levels were increased(P<0.05).Compared with LF group,mRNA expression levels of circRNA-007371 and CX3CR1 in liver tissues of low-expression circRNA-007371 group were decreased(P<0.05),liver tissue pathological injury was alleviated,and collagen protein was reduced;the levels of NLRP3,Caspase-1 and GSDMD proteins in liver tissue were decreased(P<0.05),and the serum IL-1β and IL-18 levels were decreased(P<0.05).Compared with the control group,the mRNA expression levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in HSC in over-expression group were increased(P<0.05),the protein expression levels of NLRP3,Caspase-1 and GSDMD were increased(P<0.05),and the IL-1β and IL-18 levels were increased(P<0.05).Compared with the over-expression circRNA-007371 group,the mRNA expression levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in the HSC of Antcin A group were decreased(P<0.05),the protein expression levels of NLRP3,Caspase-1 and GSDMD were decreased(P<0.05),and the contents of IL-1β and IL-18 were decreased(P<0.05). Conclusion Low expression of circRNA-007371 can alleviate LF by inhibiting pyroptosis of HSC by regulating CX3CR1.

Key words: liver fibrosis, hepatic stellate cells, circRNA-007371, CX3CR1, pyroptosis

CLC Number:

R575.2

Huang Shasha, Han Zheng, Lu Yuanyuan et al. circRNA-007371 Regulates CX3CR1 to Mediate Hepatic Stellate Cell Pyroptosis in Liver Fibrosis[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(3): 340-345.

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