title: 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-β signaling by sequestering the ligand from its receptor, but it enhances bone morphogenetic protein (BMP) signaling by promoting ligand-receptor interactions. Given the critical roles for TGF-β and BMP proteins in enhancing or suppressing renal interstitial fibrosis, respectively, we examined whether secreted KCP could attenuate renal fibrosis in mouse models of chronic and acute disease. Transgenic mice that express KCP in adult kidneys showed significantly less expression of collagen IV, α-smooth muscle 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 that were lethal for wild-type mice. 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.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Abdul
authors.initials: A
authors.lastname: Soofi
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Dressler
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D061251:Primary Cell Culture; D017434:Protein Structure, Tertiary; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D016212:Transforming Growth Factor beta; C501622:kielin-chordin-like protein, mouse
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