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

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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 −702 bp 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, in vitro. 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, in vivo. In conclusion, the −702 bp 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.

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Acknowledgment

We would like to thank Daniela Lohfink, Tanja Roth, and Melanie Scheffler for excellent technical support. This study was supported by the German Competence Network for Viral Hepatitis (HepNet), funded by the German Ministry of Education and Research (BMBF-01KI0405).

Author information

Author notes

  1. Diana Jung

    Present address: Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA

  2. Al Karim Khimji

    Present address: Internal Medicine, Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA

Authors and Affiliations

  1. Institute of Pathology, University Hospital Cologne, Koeln, Germany

    Julia Hirschfeld, Julia Maurer, Diana Jung, Monika Kwiecinski, Al Karim Khimji, Hans Peter Dienes, Jochen W. U. Fries & Margarete Odenthal

Authors
  1. Julia Hirschfeld
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  2. Julia Maurer
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  3. Diana Jung
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  4. Monika Kwiecinski
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  5. Al Karim Khimji
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  6. Hans Peter Dienes
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  7. Jochen W. U. Fries
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  8. Margarete Odenthal
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Corresponding authors

Correspondence to Jochen W. U. Fries or Margarete Odenthal.

Additional information

The first authors J. Hirschfeld and J. Maurer contributed equally to this study as well as the senior authors J. W. U. Fries and M. Odenthal.

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Hirschfeld, J., Maurer, J., Jung, D. et al. Targeting Myofibroblasts in Model Systems of Fibrosis by an Artificial α-Smooth Muscle-Actin Promoter Hybrid. Mol Biotechnol 43, 121–129 (2009). https://doi.org/10.1007/s12033-009-9186-4

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  • DOI: https://doi.org/10.1007/s12033-009-9186-4

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