Identification of differentially expressed genes during proliferative response of the liver induced by follistatin

Endocr J. 2009;56(9):1067-77. doi: 10.1507/endocrj.k09e-224. Epub 2009 Sep 5.


The liver mass is controlled strictly and maintained constant in normal and pathological situations. An exception is observed after an administration of follistatin, which induces proliferation in intact liver. In the present study, we identified genes differentially expressed in proliferating liver caused by overexpression of follistatin-288. Adenovirus vector encoding follistatin-288 (Ad-FS) or green fluorescent protein was injected intraperitoneally in rats. Changes in the liver weight, expression of follistatin and nuclear bromodeoxyuridine labeling were measured. Samples taken on day 5 and day 7 were used to prepare RNA for microarray analysis. The expression of the genes was confirmed by quantitative reverse transcriptase PCR. After the injection of Ad-FS follistatin mRNA peaked on day 3, which was followed by progressive increase in the protein expression. A peak in bromodeoxyuridine labeling was observed on day 7. Microarray data from day 5 and day 7 samples showed that follistatin modified the expression of 907 genes, of which 575 were overexpressed and 332 were downregulated taking into consideration a two fold change reference compared to control rats. In particular, significant increases and time related changes in gene expression after the Ad-FS injection were found in nine genes including growth differentiation factor 15 and fibroblast growth factor 21. This study confirmed that follistatin induced proliferation in intact liver, and identified candidate genes involved in follistatin-induced liver cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cell Proliferation*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Follistatin / biosynthesis
  • Follistatin / genetics
  • Follistatin / metabolism*
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Organ Size
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


  • Follistatin
  • Growth Differentiation Factor 15
  • RNA, Messenger
  • fibroblast growth factor 21
  • follistatin, 288-amino acid isoform
  • Fibroblast Growth Factors