Overexpression of lncRNA HEM2M alleviates liver injury in mice with non-alcoholic fatty liver disease
10.12122/j.issn.1673-4254.2024.01.01
- VernacularTitle:过表达lncRNA HEM2M改善非酒精性脂肪肝病小鼠的肝脏损伤
- Author:
Xiang KONG
1
,
2
,
3
;
Teng ZHANG
;
Yan ZHANG
;
Linxi GAO
;
Wen WANG
;
Mengyan WANG
;
Guodong WANG
;
Kun LÜ
Author Information
1. 皖南医学院非编码RNA基础与临床转化安徽省重点实验室,安徽 芜湖 241001
2. 皖南医学院弋矶山医院中心实验室,安徽 芜湖 241001
3. 皖南医学院弋矶山医院内分泌科,安徽 芜湖 241001
- Keywords:
lncRNA HEM2M;
macrophage;
non-alcoholic fatty liver disease;
pyroptosis
- From:
Journal of Southern Medical University
2024;44(1):1-8
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of long non-coding RNA(lncRNA)HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease(NAFLD).Methods Wild-type C57BL/6(WT)mice and myeloid cell-specific HEM2M knock-in(MYKI)mice were fed normal(ND)or high-fat diet(HFD)for 12 weeks.After intraperitoneal glucose tolerance and insulin tolerance tests,the mice were euthanized for detection of liver function indicators in the serum and liver tissue.HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies,and the levels of IL-6,IL-1β,and TNF-α in the liver tissues were determined with ELISA.The mRNA expressions of HEM2M and the markers of M1 macrophages(TNF-α,iNOS,and IL-6)and M2 macrophages(Arg-1,YM-1,and IL-10)were detected using qRT-PCR,and the protein expressions of P-AKT,T-AKT,NLRC4,caspase-1 and GSDMD were assayed using immunoblotting.Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay.Results Compared with HFD-fed WT mice,MYKI mice with HFD feeding showed milder liver function damage(P<0.01),alleviated hepatic steatosis,and reduced liver macrophage infiltration,glucose tolerance impairment and insulin resistance(P<0.01).The levels of IL-6,IL-1β,and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased(P<0.01)and those of M2 type markers increased(P<0.01)in the liver tissues of HFD-fed MYKI mice,which also showed reduced NLRC4 inflammasome activity,caspase-1 activation,and GSDMD-N protein expression compared with their WT counterparts(P<0.05).Conclusion Overexpression of HEM2M reduces the production of hepatic inflammatory factors,improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation,which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.
