RT Journal Article
SR Electronic
T1 Transcriptomics reveals immune-metabolism disorder in acute-on-chronic liver failure in rats
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101189
DO 10.26508/lsa.202101189
VO 5
IS 3
A1 Hozeifa M Hassan
A1 Qun Cai
A1 Xi Liang
A1 Jiaojiao Xin
A1 Keke Ren
A1 Jing Jiang
A1 Dongyan Shi
A1 Yingyan Lu
A1 Tan Li
A1 Yuxin Shang
A1 Lulu He
A1 Xi Chen
A1 Suwan Sun
A1 Peng Li
A1 Beibei Guo
A1 Jiaxian Chen
A1 Hui Yang
A1 Wen Hu
A1 Xin Chen
A1 Jun Li
YR 2022
UL https://www.life-science-alliance.org/content/5/3/e202101189.abstract
AB Acute-on-chronic liver failure (ACLF) is clinical syndrome with high mortality rate. This study aimed to perform detailed transcriptomic analysis in liver cirrhosis–based ACLF rats to elucidate ACLF pathogenesis. ACLF was induced by combined porcine serum with D-galactosamine and lipopolysaccharide. Gene expression profile of liver tissues from ACLF rats was generated by transcriptome sequencing to reveal the molecular mechanism. ACLF rats successfully developed with typical characteristics. Total of 2,354/3,576 differentially expressed genes were identified when ACLF was compared to liver cirrhosis and normal control, separately. The functional synergy analysis revealed prominent immune dysregulation at ACLF stage, whereas metabolic disruption was significantly down-regulated. Relative proportions of innate immune–related cells showed significant elevation of monocytes and macrophages, whereas adaptive immune–related cells were reduced. The seven differentially expressed genes underlying the ACLF molecular mechanisms were externally validated, among them THBS1, IL-10, and NR4A3 expressions were confirmed in rats, patient transcriptomics, and liver biopsies, verifying their potential value in the ACLF pathogenesis. This study indicates immune-metabolism disorder in ACLF rats, which may provide clinicians new targets for improving intervention strategies.