Julia Hirschfeld

Publications (2)4.34 Total impact

• Article: Targeting Myofibroblasts in Model Systems of Fibrosis by an Artificial α-Smooth Muscle-Actin Promoter Hybrid

  Julia Hirschfeld, Julia Maurer, Diana Jung, Monika Kwiecinski, Al Karim Khimji, Hans Peter Dienes, Jochen W. U. Fries, Margarete Odenthal
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  ABSTRACT: Myofibroblasts are the main cell types producing extracellular matrix proteins in a variety of fibrotic diseases. Therefore, they are useful targets for studies of intracellular communication and gene therapeutical approaches in scarring diseases. An artificial promoter containing the −702bp regulatory sequence of the α-smooth muscle actin (SMA) gene linked to the first intron enhancer sequence of the β-actin gene and the β-globin intron-exon junction was constructed and tested for myofibroblast-dependent gene expression using the green fluorescent protein as a reporter. Reporter expression revealed myofibroblast-specific function in hepatic and renal myofibroblasts, invitro. In addition, differentiation-dependent activation of the SMA-β-actin promoter hybrid was shown after induction of myofibroblastic features in mesangial cells by stretching treatment. Furthermore, wound healing experiments with SMA-β-actin promoter reporter mice demonstrated myofibroblast-specific action, invivo. In conclusion, the −702bp regulatory region of the SMA promoter linked to enhancing β-actin and β-globin sequences benefits from its small size and is suggested as a promising tool to target myofibroblasts as the crucial cell type in various scarring processes.
  Molecular Biotechnology 04/2012; 43(2):121-129. · 2.17 Impact Factor
• Article: Targeting myofibroblasts in model systems of fibrosis by an artificial alpha-smooth muscle-actin promoter hybrid.

  Julia Hirschfeld, Julia Maurer, Diana Jung, Monika Kwiecinski, Al Karim Khimji, Hans Peter Dienes, Jochen W U Fries, Margarete Odenthal
  [show abstract] [hide abstract]
  ABSTRACT: Myofibroblasts are the main cell types producing extracellular matrix proteins in a variety of fibrotic diseases. Therefore, they are useful targets for studies of intracellular communication and gene therapeutical approaches in scarring diseases. An artificial promoter containing the -702 bp regulatory sequence of the alpha-smooth muscle actin (SMA) gene linked to the first intron enhancer sequence of the beta-actin gene and the beta-globin intron-exon junction was constructed and tested for myofibroblast-dependent gene expression using the green fluorescent protein as a reporter. Reporter expression revealed myofibroblast-specific function in hepatic and renal myofibroblasts, in vitro. In addition, differentiation-dependent activation of the SMA-beta-actin promoter hybrid was shown after induction of myofibroblastic features in mesangial cells by stretching treatment. Furthermore, wound healing experiments with SMA-beta-actin promoter reporter mice demonstrated myofibroblast-specific action, in vivo. In conclusion, the -702 bp regulatory region of the SMA promoter linked to enhancing beta-actin and beta-globin sequences benefits from its small size and is suggested as a promising tool to target myofibroblasts as the crucial cell type in various scarring processes.
  Molecular Biotechnology 07/2009; 43(2):121-9. · 2.17 Impact Factor