Uteroglobin: Physiological role in normal glomerular function uncovered by targeted disruption of the uteroglobin gene in mice

A. B. Mukherjee*, G. C. Kundu, A. K. Mandal, N. Pattabiraman, Chiun-Jye Yuan, Z. Zhang

*此作品的通信作者

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

摘要

Blastokinin or uteroglobin (UG) is an evolutionarily conserved, steroid- inducible, homodimeric, multifunctional, secreted protein with potent immunomodulatory/antiinflammatory properties. Recently, a UG-receptor expressed on several malignant and normal cell types has been characterized. Although the biochemistry, structural, and molecular biology of UG have been extensively studied, its physiological function(s), until recently, remained unknown. By generating UG-null (UG(-/-)) mice, we determined that an essential role of UG is to prevent severe renal disease caused by an abnormal deposition of predominantly multimeric fibronectin (Fn) and collagen in the glomerulus. The molecular mechanisms by which UG prevents this disease in control (UG(+/+)) mice, at least in part, is attributable to its high- affinity binding to Fn and the formation of Fn-UG heteromers, which counteract both Fn-Fn and Fn-collagen interactions, required for abnormal tissue deposition. In addition, by inhibiting secretory phospholipase A2 (sPLA2) activity and decreasing the level of lysophosphatidic acid (LPA), UG may indirectly prevent the activation of integrins (eg, α5β1) that enhance abnormal tissue deposition of Fn. The mechanism(s) of UG action is likely to be even more complex, because it also functions through a receptor- mediated pathway that has not yet been clearly defined. Nevertheless, the UG gene-knockout mice provide a valuable animal model for investigation of human glomerulopathies in general and familial Fn-deposit glomerulopathy in particular.

原文English
頁(從 - 到)1106-1120
頁數15
期刊American Journal of Kidney Diseases
32
發行號6
DOIs
出版狀態Published - 1 1月 1998

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