Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic disease - PubMed (original) (raw)

doi: 10.1038/nm1217. Epub 2005 Mar 27.

Affiliations

PMID: 15793581
DOI: 10.1038/nm1217

Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic disease

Jingmei Lin et al. Nat Med. 2005 Apr.

Abstract

The 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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Comment in

Setting a trap for tissue fibrosis.
Neilson EG. Neilson EG. Nat Med. 2005 Apr;11(4):373-4. doi: 10.1038/nm0405-373. Nat Med. 2005. PMID: 15812511 No abstract available.

Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic disease - PubMed (original) (raw)