title: Short- or long-term effects of a low-protein diet on fibronectin and transforming growth factor-beta synthesis in Adriamycin-induced nephropathy.
abstract: Increased synthesis and gene expression of fibronectin or transforming growth factor-beta (TGF-beta) have been reported to be involved in the progressive process of doxorubicin hydrochloride (Adriamycin)-induced nephropathy. In the present study, the effects of dietary protein restriction on the synthesis and gene expression of fibronectin or TGF-beta were investigated by immunoprecipitation, Northern blotting, and TGF-beta bioassay in this model after subjects were given either short- or long-term low-protein diets. In the long-term diet experiment, either a normal protein diet (NPD, 20%) or low-protein diet (LPD, 5%) was fed to the Adriamycin rats for 8 weeks after the injection of Adriamycin. An 8-week LPD significantly ameliorated kidney destruction and remarkably reduced the fibronectin synthesis. Furthermore, the significant decreases of the latent TGF-beta secretion and the expression of TGF-beta 1 mRNA were observed in the Adriamycin rats fed an 8-week LPD. In the short-term diet experiment, an NPD or LPD was fed to the Adriamycin rats for 2 weeks at weeks 4, 8, or 16 after the injection of Adriamycin. A 2-week LPD did not ameliorate kidney damage. Although fibronectin synthesis by the renal cortex in the Adriamycin rats was remarkably reduced by a 2-week LPD, there was no significant decrease in the latent TGF-beta secretion in the Adriamycin rats. The mRNA expressions of fibronectin or TGF-beta 1 were not affected by a 2-week LPD in the Adriamycin rats at any stage. In conclusion, decreased fibronectin and TGF-beta synthesis may be one of the mechanisms by which the long-term dietary protein restriction ameliorates kidney damage. On the other hand, a 2-week LPD affected the only fibronectin synthesis, which thus suggested that an LPD might exert a quicker influence on the protein synthesis of fibronectin than on the transcriptional events of fibronectin.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.forename: S
authors.initials: S
authors.lastname: Okuda
authors.forename: K
authors.initials: K
authors.lastname: Tamaki
authors.forename: M
authors.initials: M
authors.lastname: Fujishima
mesh_terms: D000818:Animals; D001681:Biological Assay; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D004317:Doxorubicin; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004044:Dietary Proteins; D005353:Fibronectins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004317:Doxorubicin