PT  - JOURNAL ARTICLE
AU  - Hozeifa M Hassan
AU  - Qun Cai
AU  - Xi Liang
AU  - Jiaojiao Xin
AU  - Keke Ren
AU  - Jing Jiang
AU  - Dongyan Shi
AU  - Yingyan Lu
AU  - Tan Li
AU  - Yuxin Shang
AU  - Lulu He
AU  - Xi Chen
AU  - Suwan Sun
AU  - Peng Li
AU  - Beibei Guo
AU  - Jiaxian Chen
AU  - Hui Yang
AU  - Wen Hu
AU  - Xin Chen
AU  - Jun Li
TI  - Transcriptomics reveals immune-metabolism disorder in acute-on-chronic liver failure in rats
AID  - 10.26508/lsa.202101189
DP  - 2022 Mar 01
TA  - Life Science Alliance
PG  - e202101189
VI  - 5
IP  - 3
4099  - https://www.life-science-alliance.org/content/5/3/e202101189.short
4100  - https://www.life-science-alliance.org/content/5/3/e202101189.full
SO  - Life Sci. Alliance2022 Mar 01; 5
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.