NAGASAWA Ryuji Saitama Medical Center, Lecturer, 医学部, 講師 (70146794)
UTSUNOMIYA Yasunori Jikei University School of Medicine, Assistant, 医学部, 助手 (70231181)
KAWAMURA Tetsuya Jikei University School of Medicine, Lecturer, 医学部, 講師 (20161367)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1994 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1993 : ¥1,700,000 (Direct Cost : ¥1,700,000)
1. Identification and characterization of tyrosine kinases expressed in glomerular cells.
We isolated and identified the tyrosine kinase genes by RT-PCR with degenerate primers from messenger RNA prepared from isolated glomeruli, cultured mesangial cells and cultured glomerular endthelial cells. Sequence analysis of PCR-amplified cDNAs resulted in the isolation of 24 tyrosine kinases. We showed for the first time the constitutive expression of 15 tyrosine kinases ; tyro-1, tyro-4, tyro-6, hyk, Ptk-3, Ryk, tie, yes, lyn, tec, Jak1, Jak2, Jak3, c-abl, and flk, in renal glomeruliin addition to the previously known renal expressions of 7 tyrosine kinases ; IGFR,Trk B,PDGFR,Flt-1, Flk-1, bFGFR,and Ufo.
2.Functional role of Flt-1 expressed in glomerular mesangial cells.
We showed that, Flt-1, an endothelial cell-specific receptor-type tyrosine kinase for vascular endotherial growth factor (VEGF), is expressed in renal mesangial cells. We further investigated its gene expression in cultured mesangial cells upon the stimulation of PDGF with the concomitant up-regulation of VEGF.These data suggest the possible involvement of VEGF/Flt-1 system in cytokine-induced mesangial cell proliferations.
3.Neonatal thymectomy diminished renal IgA deposition in IgA nephropathy-prone ddY mice.
To clarify the role of T cells on mesangial IgA deposition in the kidney of ddY mice, we investigated the IgA deposition in neonatally thymectomized ddY mice. Although the thymectomized mice developed a renal lesion closely resembling that typical of IgAN,the extent of their mesangial IgA deposition was significantly milder than in control sham-operated mice. The percentage of splenic T cells and the magnitude of mitogenic responses both decreased markedly in thymectomized compared with control mice. The results suggest that thymus-derived T cells or their products determine the amount of IgA deposition in the kidney of ddY mice.