Molecular mechanism of epithelialization by non-peptide, endogenous siderophores

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Neutrophil gelatinase-associated lipocalin (Ngal or LCN2) has a renoprotective activity, which is enhanced by the presence of enterochelin, an E. coli-derived siderophore [Mori et al. J Clin Invest 2005]. Purification of mammalian siderophores lead to identification of catechol and its derivatives [Bao et al. Nat Chem Biol 2010]. Catechol largely affects tissue distribution of iron in mammals. Ngal plays a renoprotective role in renal ischemia-reperusion injury, whereas enhances renal hypertrophy and kidney injury in 3/4 subtotal nephrectomy [Viau et al. J Clin Invest 2005]. Urinary Ngal levels are determined by renal synthesis, release from neutrophils, and impaired reabsorption at proximal tubules [Kuwabara et al. Kidney Int 2009]. Urinary Ngal is useful for the evaluation of disease severity and treatment efficacy of chronic kidney disease [Kasahara et al. Nephrol Dial Trasplant 2009]. Ngal reporter mice allow real-time visualization of spaciotemporal regulation of Ngal expression, and its changes by treating reagents [Paragas et al. Nat Med 2011].