title: Gene expression profiles during hepatic stellate cell activation in culture and in vivo.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Samuele
authors.initials: S
authors.lastname: De Minicis
authors.forename: Ekihiro
authors.initials: E
authors.lastname: Seki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchinami
authors.forename: Johannes
authors.initials: J
authors.lastname: Kluwe
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
authors.forename: David A
authors.initials: DA
authors.lastname: Brenner
authors.forename: Robert F
authors.initials: RF
authors.lastname: Schwabe
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000293:injuries / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D000199:Actins; D024042:Collagen Type I; D018972:Insulin-Like Growth Factor Binding Protein 3; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C512906:Ogn protein, mouse; D002251:Carbon Tetrachloride