Histone Deacetylases In Hepatic Stellate Cells: a Preliminary Study

Nele Nuytten, Inge Mannaerts, Albert Geerts, Leonardus Van Grunsven

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)Research


Introduction: Transdifferentiation of hepatic stellate cells (HSC) to myofibroblastic cells is
a central event in liver fibrogenesis. Understanding molecular mechanisms that underlie
this cellular event provides pivotal insights into development of new therapeutic
modalities for cirrhosis. Stellate cell activation by liver injury leads to a phenotypic
transdifferentiation characterized by loss of vitamin A and extensive production of
extracellular matrix. This process can be mimicked in vitro by culturing freshly isolated
hepatic stellate cells. The use of the histone deacetylase inhibitor (HDAC-I) Trichostatin
A (TSA) in these cultures has shown that histone deacetylases might play a role in the
pathogenesis of liver fibrosis. Short-term treatment of rat HSC with TSA decreases the
transcription of alpha smooth muscle actin (αSMA) and collagen III and influences
actin filament formation. In this study we want to address the presence, activity and
importance of the different HDACs during mouse HSC transdifferentiation
Material and methods: To investigate the possibility of liver- or HSC-specific HDACs,
mRNA levels of HDACs were determined in isolated HSC as well as in liver, kidney,
brain, pancreas, heart and muscle from Balb/c mice by reverse transcriptase quantitative
polymerase chain reaction (RT-qPCR). This technique was also used to study the HDAC
expression profile during HSC activation in vitro. Furthermore, we analyzed the
sensitivity of different markers for activated stellate cells for different HDAC-Is. We
currently focus on valproic acid because of its stability and its specificity.
Results: RT-qPCR showed neither liver- nor HSC-specific HDAC mRNAs. The HDAC
mRNA profile during transdifferentiation of freshly isolated hepatic stellate cells in culture
was not altered. Transcription of several stellate cell transdifferentiation markers is
inhibited by long term treatment of different HDAC-Is such as smooth muscle alfa-actin
(Acta2), smooth muscle myosin (SMMy1), lysyl oxidase (Lox) and secreted
phosphoprotein 1 (Spp1).
Conclusions: We have confirmed in mouse HSC cultures that different HDAC-Is can
influence the transdifferentiation from quiescent to activated HSCs. Several markers
have been identified that can be used to monitor this process in future RNA interference
experiments. This will enable us to identify the HDAC(s) and HDAC complexes that are
involved in the activation of HSC in vitro but also in vivo.
Original languageEnglish
Title of host publicationProceedings 2007 BSCDB Spring meeting
Publication statusPublished - 2007
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009


ConferenceFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet


  • liver fibrosis
  • stellate cells
  • histone deacetylases

Fingerprint Dive into the research topics of 'Histone Deacetylases In Hepatic Stellate Cells: a Preliminary Study'. Together they form a unique fingerprint.

Cite this