The severity of renal lesions after nephron reduction varied substantially among mouse strains and required activation of EGFR. Lipocalin 2 (Lcn2, also known as neutrophil gelatinase–associated lipocalin [NGAL]), the most highly upregulated gene in a mouse strain which develop severe renal lesions, is not simply a marker of renal lesions, but also an active player in disease progression. The severity of renal lesions was dramatically reduced in Lcn2–/– mice. Lcn2 expression increases upon EGFR activation and Lcn2 mediates its mitogenic effect during renal deterioration. EGFR inhibition prevented Lcn2 upregulation and lesion development in mice expressing a dominant negative EGFR isoform. Cell proliferation was dramatically reduced in Lcn2–/–mice. LCN2 is increased particularly in patients who rapidly progressed to end-stage renal failure.rnrnScientific Publication(s):rnJ Clin Invest., 2010 November 1, Viau A. et al., Lipocalin 2 is essential for chronic kidney disease progression in mice and humans, doi: 10.1172/JCI42004