title: Fibronectin turnover in human mesangial cell cultures as affected by adriamycin.
abstract: Fibronectin (FN) turnover and turnover changes induced by the anticancer drug Adriamycin (ADR) were measured in human mesangial cells (HMC) in vitro. HMC cultures synthesize cellular FN (2.2 +/- 0.3% of total protein synthesis; n = 12) which is secreted and incorporated into a fibrillar extracellular matrix (ECM). A 24 hr incubation of HMC with ADR (0.5-5 micrograms/ml) resulted in an accumulation of FN in the culture medium, with a maximum increase following 5 micrograms/ml (7.3 +/- 2.3 pg/cell vs. controls: 4.4 +/- 1.9 pg/cell; n = 10). Correspondingly, radioactively labeled immunoprecipitable FN was increased in a dosage-dependent manner in the culture medium up to 50% vs. controls. The incorporation of radioactively labeled FN into ECM was significantly increased following 2 micrograms ADR/ml. In accordance, immunofluorescence staining revealed an expansion of pericellular FN fibers in cultures exposed to 2 micrograms ADR/ml. Concomitant with the accumulation of extracellular FN, radioactively labeled FN in the cells was reduced by 22%. Qualitative characterization of FN patterns revealed a diminished number of degradation products in the culture medium of ADR-treated HMC. These data suggest that ADR interferes with the turnover of FN secreted by HMC in vitro in such a way that FN accumulates extracellularly. This in turn leads to a reduced FN synthesis. These findings are compatible with a loss of urinary FN degradation products accompanying the onset of proteinuria in ADR-treated rats.
authors.affiliation: Institute of Animal Physiology, Justus-Liebig-University Giessen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Soose
authors.forename: S
authors.initials: S
authors.lastname: Wenzel
authors.forename: H
authors.initials: H
authors.lastname: Stolte
mesh_terms: D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D011233:Precipitin Tests
chemical_list: D003470:Culture Media; D005353:Fibronectins; D004317:Doxorubicin