Localization of Smad6 and Smad7 in the Rat Kidney and Their Regulated Expression in the Anti-Thy-1 Nephritis

摘要

Under normal conditions, kidney expresses Smadl and Smad7 most abundantly among the organs of th, body. To understand the physiological roles of thesl Smad expressions in the kidney, we first identified th, sites of Smad6 and Smad 7 expression in the rat kidne: by in situ hybridization. The expression of Smad7 iJ the rat kidney was only observed in the glomeruli while Smad6 was expressed in both the glomeruli anc thick ascending limb of Henle's loop. In order to inves tigate whether Smad6 and 7 are also involved in th4 negative feedback loop of TGF-fJ signaling in vivo, W4 examined the changes of mRNA levels of these Smad: in the glomeruli of rat anti-Thy1 (1-22-3) nephritis, ~ model where the expression ofTGF-fJ in the glomerul has been shown to be most up-regulated from day 4 t. 14 after the antibody injection. Unexpectedly, 7 day: after injection, the levels of Smad6 and Smad7 did no increase but rather decreased to -70% of the levels 01 day 0. During that period, Smad7 immunostaining wal observed in the glomerular endothelial cells (GEN where Smad3 immunostaining was also observed. Thil suggested that Smad7 expression was not augmente( by the TGF-fJ signal in GEN in vivo in anti-Thy-1 ne phritis. The absence of up-regulation of these inhibi tory Smads may be involved in the pathogenesis 0 anti-Thv-1 nenhritis.