Gene expression profiles during hepatic stellate cell activation in culture and in vivo

Gastroenterology. 2007 May;132(5):1937-46. doi: 10.1053/j.gastro.2007.02.033. Epub 2007 Feb 21.


Background & aims: Following hepatic injury, hepatic stellate cells (HSCs) transdifferentiate to become extracellular matrix-producing myofibroblasts and to promote hepatic fibrogenesis. In this study, we determine gene expression changes in 3 different models of HSC activation and investigate whether HSC culture activation reproduces gene expression changes of HSC in vivo activation.

Methods: HSCs were isolated by density centrifugation and magnetic antibody cell sorting from normal mice, CCl(4)-treated mice, and mice that underwent bile duct ligation (BDL). Gene expression was analyzed by microarray and confirmed by polymerase chain reaction and Western blot analysis.

Results: Two thousand seventy-three probe sets were differentially expressed in at least 1 of 3 models of HSC activation, including novel genes that encode proinflammatory and antiapoptotic mediators; transcription factors; cell surface receptors; and cytoskeleton components such as CXCL14, survivin, septin 4, osteopontin, PRX1, LMCD1, GPR91, leiomodin, and anillin. BDL- and CCl(4)-activated HSCs showed highly correlated gene expression patterns, whereas culture activation only partially reproduced the gene expression changes observed during BDL- and CCl(4)-induced activation. Coculture with Kupffer cells or lipopolysaccharide treatment during culture activation shifted the expression of most examined genes toward the pattern observed during in vivo activation, suggesting a role for these factors in the microenvironment that drives HSC activation.

Conclusions: The almost identical HSC gene expression patterns after BDL or CCl(4) treatment indicate that HSCs exert similar functions in different types of liver injury. Because culture activation does not properly regulate gene expression in HSCs, in vivo activation should be considered the gold standard for the study of HSC biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Carbon Tetrachloride / pharmacology
  • Cells, Cultured
  • Coculture Techniques
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kupffer Cells / cytology
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism*
  • Ligation
  • Lipopolysaccharides / pharmacology
  • Liver / injuries
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotide Array Sequence Analysis


  • Actins
  • Collagen Type I
  • Insulin-Like Growth Factor Binding Protein 3
  • Intercellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Ogn protein, mouse
  • Carbon Tetrachloride