Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury
Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury
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DOI：
10.1038/sj.ki.5002626
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发表时间：
2008-01-01
影响因子：
19.6
通讯作者：
Yanagita, M.
中科院分区：
文献类型：
--
作者：
Tanaka, M.;Endo, S.;Yanagita, M.
一旦发生终末期肾病，任何现有的治疗方法都无法逆转。然而，骨形态发生蛋白-7(BMP-7)是逆转终末期肾病的一种可能的治疗方法。此前，我们发现BMP拮抗剂子宫增敏相关基因-1(USAG-1，也称为胞外蛋白和硬化素结构域包含1)负向调节BMP-7的肾脏保护作用。在此，我们发现在肾脏发育的后期，USAG-1和BMP-7的表达比例显著增加，USAG-1仅在分化的远端小管与BMP-7的表达重叠。USAG-1在发育中肾脏中的表达检测表明，近端和远端小管标记阳性细胞镶嵌在未成熟肾单位中。这表明，每个细胞都控制着自己成为近端或远端小管细胞的命运。在肾损伤模型中，USAG-1/BMP-7的表达比率随着肾脏损伤而降低，但在随后的肾脏再生后增加。我们的研究表明，肾活检组织中USAG-1的表达可能有助于预测预后。
Once developed, end-stage renal disease cannot be reversed by any current therapy. Bone morphogenetic protein-7 (BMP-7), however, is a possible treatment for reversing end-stage renal disease. Previously, we showed that the BMP antagonist uterine sensitization-associated gene-1 (USAG-1, also known as ectodin and sclerostin domain-containing 1) negatively regulates the renoprotective action of BMP-7. Here, we show that the ratio between USAG-1 and BMP-7 expression increased dramatically in the later stage of kidney development, with USAG-1 expression overlapping BMP-7 only in differentiated distal tubules. Examination of USAG-1 expression in developing kidney indicated that a mosaic of proximal and distal tubule marker-positive cells reside side by side in the immature nephron. This suggests that each cell controls its own fate for becoming a proximal or distal tubule cell. In kidney injury models, the ratio of USAG-1 to BMP-7 expression decreased with kidney damage but increased after subsequent kidney regeneration. Our study suggests that USAG-1 expression in a kidney biopsy could be useful in predicting outcome.