RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice

Kyuwon Lee, Hyeonju Yu, Stephanie Shouse, Byungwhi Kong, Jihye Lee, Seong Ho Lee, Kwang Suk Ko

Research output: Contribution to journalArticlepeer-review

Abstract

Prohibitin 1 (PHB1) is an evolutionarily conserved and ubiquitously expressed protein that stabilizes mitochondrial chaperone. Our previous studies showed that liver-specific Phb1 deficiency induced liver injuries and aggravated lipopolysaccharide (LPS)-induced innate immune responses. In this study, we performed RNA-sequencing (RNA-seq) analysis with liver tissues to investigate global gene expression among liver-specific Phb1−/−, Phb1+/−, and WT mice, focusing on the differentially expressed (DE) genes between Phb1+/− and WT. When 78 DE genes were analyzed for biological functions, using ingenuity pathway analysis (IPA) tool, lipid metabolism-related genes, including insulin receptor (Insr), sterol regulatory element-binding transcription factor 1 (Srebf1), Srebf2, and SREBP cleavage-activating protein (Scap) appeared to be downregulated in liver-specific Phb1+/− compared with WT. Diseases and biofunctions analyses conducted by IPA verified that hepatic system diseases, including liver fibrosis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death, which may be caused by hepatotoxicity, were highly associated with liver-specific Phb1 deficiency in mice. Interestingly, of liver disease-related 5 DE genes between Phb1+/− and WT, the mRNA expressions of forkhead box M1 (Foxm1) and TIMP inhibitor of metalloproteinase (Timp1) were matched with validation for RNA-seq in liver tissues and AML12 cells transfected with Phb1 siRNA. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with hepatic Phb1.

Original languageEnglish
Article number717911
JournalFrontiers in Physiology
Volume12
DOIs
StatePublished - 3 Sep 2021

Keywords

  • RNA-seq
  • gene expression
  • hepatotoxicity
  • liver disease
  • prohibitin 1

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