Do ASARM peptides play a role in nephrogenic systemic fibrosis?

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Publisher: American Physiological Society
Document Type: Author abstract
Length: 232 words

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Abstract :

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium ([Gd.sup.3+])-based contrast agents (GBCAs) in patients with kidney disease. The release of toxic [Gd.sup.3+] from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of [Gd.sup.3+] release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE-associated peptides (ASARM peptides) induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind [Ca.sup.2+] and hydroxyapatite. Since the ionic radius of [Gd.sup.3+] is close to that of [Ca.sup.2+], we hypothesized that ASARM peptides increase the risk of NSF by inducing release of [Gd.sup.3+] from GBCAs. Flere, we show 1) ASARM peptides bind and induce release of [Gd.sup.3+] from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the [Gd.sup.3+]-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-like pathology in a murine model with increased ASARM peptide (Hyp mouse). We conclude ASARM peptides may play a role in NSF and SPR4 peptide is a candidate adjuvant for preventing or reducing risk of disease. nephrogenic system fibrosis; chronic kidney disease; osteopontin; MEPE; DMP1; FGF23; PHEX; sclerostin doi: 10.1152/ajprenal.00201.2015.

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Gale Document Number: GALE|A438626250