Kielin/Chordin-like protein attenuates both acute and chronic renal injury

Abstract

The secreted kielin/chordin-like (KCP) protein, one of a family of cysteine-rich proteins, suppresses TGF-b signaling by sequestering the ligand fromits receptor, but it enhances bone morphogenetic protein (BMP) signaling by promoting ligand-receptor interactions.Given the critical roles for TGF-b and BMP proteins in enhancing or suppressing renal interstitial fibrosis, respectively, we examined whether secreted KCP could attenuate renal fibrosis inmousemodels of chronic and acute disease. Transgenicmice that express KCP in adult kidneys showed significantly less expression of collagen IV, a-smoothmuscle actin, and other markers of disease progression in the unilateral ureteral obstruction model of renal interstitial fibrosis. In the folic acid nephrotoxicity model of acute tubular necrosis, mice expressing KCP survived high doses of folic acid thatwere lethal forwild-typemice. With a lower dose of folic acid,mice expressing KCP exhibited improved renal recovery compared with wild-type mice. Thus, these data suggest that extracellular regulation of the TGF-β/BMP signaling axis by KCP, and by extension possibly other cysteine-rich domain proteins, can attenuate both acute and chronic renal injury. Copyright © 2013 by the American Society of Nephrology.