Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome
スポンサーリンク
概要
- 論文の詳細を見る
腎不全治療の新しい可能性の発見－腎不全をきたす遺伝病、アルポート症候群はBMP阻害分子USAG-1欠損によって軽快し、腎不全に陥らない－. 京都大学プレスリリース. 2010-02-09. http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2009/100209_1.htmThe glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and causeAlport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization–associated gene-1(USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3–/– mice, which model Alport syndrome. Ablation of Usag1 in Col4a3–/– mice led to substantial attenuation of disease progression,normalization of GBM ultrastructure, preservation of renal function, and extension of life span.Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in thedistal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute toGBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3–/– mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promisingtherapeutic approach for the treatment of Alport syndrome.
- 2010-02-08
論文 | ランダム
- 242.種々の負荷強度における下腿三頭筋の疲労経過に伴う筋電図変化
- 61.局所冷却および温熱条件負荷による下腿三頭筋収縮の疲労経過
- 通所授産施設に於けるHD患者(chronic hemodialysis patients)の有酸素作業能と運動強度
- 29.目標からの位置と投運動の制御能力
- 53.筋肉痛および遅発性筋肉痛の回復に及ぼすアイシングの効果