Short-or long-term effects of a low-protein diet on fibronectin and transforming growth factor-β synthesis in Adriamycin-induced nephropathy(アドリアマイシン腎症における短期および長期の低蛋白食投与の効果 -フィブロネクチンおよびtransforming growth factor(TGF)-β産生について)

Increased synthesis and gene expression of fibronectin or transforming growth factor-� (TGF-�) 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-� were investigated by immunoprecipitation, Northern blotting, and TGF-� 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-� secretion and the expression of TGF-� 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-� secretion in the Adriamycin rats.The mRNA expressions of fibronectin or TGF-� 1 were not affected by a 2-week LPD in the Adriamycin rats at any stage.In conclusion, decreased fibronectin and TGF-� synthesis may be one of the mech anisms by which the long-term dietary protein restriction ameliorates kidney dam age.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.(J lAs CuN MEo 1996; 127:29-39) Abbreviations: DMEM = Dulbecco's modified Eagle medium; ECM =extracellular matrix: FGS = focal glomerular sclerosis: IGF = insulin-like growth factor: LPD = low protein diet: NPD = normal protein diet; SDS = sodium dodecylsulfate: SSC