Tóm tắt
Abstract: Dialysis dependency is one of the leading causes of morbidity and mortality in the world, and once end‐stage renal disease develops, it cannot be reversed by currently available therapy. Although the administration of large dose of bone morphogenetic protein‐7 (BMP‐7) has been shown to repair established renal injuries and improves renal function, pathophysiological role of endogenous BMP‐7 and regulatory mechanism of its activities remain elusive. Here we show that uterine sensitization‐associated gene‐1 (USAG‐1), novel BMP antagonist abundantly expressed in the kidney, is the central negative regulator of BMP function in the kidney, and that mice lacking USAG‐1 (USAG‐1−/− mice) are resistant to kidney injuries. USAG‐1−/− mice exhibited prolonged survival and preserved renal function in acute and chronic renal injuries. Renal BMP signaling, assessed by phosphorylation of Smad proteins, is significantly enhanced in USAG‐1−/− mice during renal injury, indicating that the preservation of renal function is attributed to enhancement of endogenous BMP signaling. Furthermore, the administration of neutralizing antibody against BMP‐7 abolished reno‐protection in USAG‐1−/− mice, indicating that USAG‐1 plays a critical role in the modulation of reno‐protective action of BMP, and that inhibition of USAG‐1 will be promising means of development of novel treatment for kidney diseases.
