Nature Medicine
11, 387 - 393 (2005)
Published online: 27 March 2005; | doi:10.1038/nm1217
Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic diseaseJingmei Lin1, Sanjeevkumar R Patel2, Xu Cheng3, Eun Ah Cho1, Inna Levitan1, Matthew Ullenbruch1, Sem H Phan1, John M Park3
& Gregory R Dressler11
Department of Pathology, University of Michigan, 1301 Catherine Street, Ann Arbor, Michigan 48109, USA. 2
Department of Internal Medicine, University of Michigan, 3110 Taubman, Ann Arbor, Michigan 48109, USA. 3
Department of Urology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Correspondence should be addressed to Gregory R Dressler dressler@umich.eduThe bone morphogenetic proteins (BMPs) profoundly affect embryonic development, differentiation and disease. BMP signaling is suppressed by cysteine-rich domain proteins, such as chordin, that sequester ligands from the BMP receptor. We describe a novel protein, KCP, with 18 cysteine-rich domains. Unlike chordin, KCP enhances BMP signaling in a paracrine manner. Smad1-dependent transcription and phosphorylated Smad1 (P-Smad1) levels are increased, as KCP binds to BMP7 and enhances binding to the type I receptor. In vivo, Kcp-/- mice are viable and fertile. Because BMPs have a pivotal role in renal disease, we examined the phenotype of Kcp-/- mice in two different models of renal injury. Kcp-/- animals show reduced levels of P-Smad1, are more susceptible to developing renal interstitial fibrosis, are more sensitive to tubular injury and show substantial pathology after recovery. The data indicate an important role for KCP in attenuating the pathology of renal fibrotic disease.
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