@article{oai:kanazawa-u.repo.nii.ac.jp:00013423,
 author = {Tanaka, Mari and Asada, Misako and Higashi, Atsuko Y. and Nakamura, Jin and Oguchi, Akiko and Tomita, Mayumi and Yamada, Sachiko and Asada, Nariaki and Takase, Masayuki and Okuda, Tomohiko and Kawachi, Hiroshi and Economides, Aris N. and Robertson, Elizabeth and Takahashi, Satoru and Sakurai, Takeshi and Goldschmeding, Roel and Muso, Eri and Fukatsu, Atsushi and Kita, Toru and Yanagita, Motoko},
 issue = {3},
 journal = {Journal of Clinical Investigation},
 month = {Mar},
 note = {The 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 cause Alport 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 the distal 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 to GBM 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 promising therapeutic approach for the treatment of Alport syndrome., 金沢大学医薬保健研究域医学系},
 pages = {768--777},
 title = {Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome},
 volume = {120},
 year = {2010}
}