Postmitotic differentiation of rat lung fibroblasts: induction by bleomycin and effect on prolyl 4-hydroxylase

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie
Roland KoslowskiM Kasper

Abstract

The cytostatic drug bleomycin (BLM) induces pulmonary fibrosis as its main side effect. Fibroblasts in fibrotic foci are the main cellular source for extracellular matrix accumulation that typifies fibrosis. In vitro studies demonstrated the ability of cytotoxic drugs to induce terminal differentiation of fibroblasts. These postmitotic cells are very active in regard to production of collagens. The present study was addressed to investigate the potential of BLM to induce terminal differentiation of rat lung fibroblasts in vitro and the consequences for collagen production and for the expression and activity of the collagen modifying enzyme prolyl 4-hydroxylase (P4H). The BLM effects were compared with those of mitomycin C (MMC), another cytotoxic agent with known potential for initiation of postmitotic differentiation of fibrobasts. BLM induced postmitotic differentiation of rat lung fibroblasts. The capacity of the cells to form clones was diminished by BLM or MMC in a concentration dependent manner. Both drugs initiated the formation of an increasing number of postmitotic cell clones. The postmitotic differentiation was accompanied by an increase in total collagen production by the cells. Administration of BLM to cultures of ...Continue Reading

References

Jun 1, 1992·Analytical Biochemistry·B J WalshS N Breit
Nov 1, 1986·The Journal of Clinical Investigation·P L MoseleyG W Hunninghake
Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·K BayreutherP I Francz
Sep 17, 2002·American Journal of Respiratory and Critical Care Medicine·Sushmita GhoshGilbert F Morris
Oct 1, 2003·The European Respiratory Journal·R KoslowskiM Kasper

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Citations

Jun 13, 2009·American Journal of Respiratory Cell and Molecular Biology·Yongju LuYon Rojanasakul

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