Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin.
Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin.
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DOI：
10.1126/science.276.5317.1408
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发表时间：
1997-05
期刊：
影响因子：
56.9
通讯作者：
Zhongjian Zhang;Gopal C. Kundu;C. Yuan;Jerrold M. Ward;Eric J. Lee;F. DeMayo;Heiner Westphal;Anil B. Mukherjee
中科院分区：
文献类型：
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作者：
Zhongjian Zhang;Gopal C. Kundu;C. Yuan;Jerrold M. Ward;Eric J. Lee;F. DeMayo;Heiner Westphal;Anil B. Mukherjee
尽管子宫珠蛋白（UG）（一种类固醇诱导的分泌蛋白）具有多种生物活性，但其生理功能尚不清楚。子宫珠蛋白基因被破坏的小鼠患有严重的肾脏疾病，这与主要是多聚体纤连蛋白（Fn）的大量肾小球沉积有关。通常阻止 Fn 沉积的分子机制似乎涉及 UG 与 Fn 的高亲和力结合，形成 Fn-UG 异聚体，从而抵消 Fn 自聚集，这是异常组织沉积所必需的。因此，UG 对于维持小鼠正常肾功能至关重要，这提出了类似的致病机制可能是遗传性 Fn 沉积人类肾小球疾病的可能性。
Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn). The molecular mechanism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation, which is required for abnormal tissue deposition. Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease.