High expression of neutrophil gelatinase-associated lipocalin (NGAL) in the kidney proximal tubules of diabetic rats

Purpose: Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) plays important roles in many physiological and pathological processes including diabetic nephropathy (DN), in which a markedly increasing in NGAL levels in patient's serum and urine has been reported. This study investigated the expression of NGAL in the kidney of diabetic rats. Materials/methods: Sixty-four Sprague Dawley rats were randomly divided into 2 groups: non-diabetic control groups and diabetic groups. Diabetes was induced by intraperitoneal injection of streptozotocin. Relevant indicators were separately evaluated 2, 4, 8 and 12 weeks after induction of diabetes. Results: In the diabetic groups, urinary NGAL values were markedly increased even before the appearance of pathological albuminuria. Moreover, diabetic rats showed significant upregulation of NGAL mRNA expression starting at week 2 (1.0 +/- 0.03 vs. 3.09 +/- 0.40, NGAL/beta-actin. P < 0.05), while the increase of NGAL protein expression appeared subsequently (0.58 +/- 0.03 vs. 0.65 +/- 0.01, NGAL/beta-actin, P < 0.05). At the end of week 12, kidney NGAL mRNA and protein levels were increased to 5.95-fold and 1.24-fold of the control groups, respectively. Observable ultrastructural alterations of renal tubules were not detected until week 4, while pathological changes gradually became apparent in the course of the study. Strong positive immunohistochemical staining of NGAL was visualized in the proximal tubular cells of diabetic rats at week 12. Conclusions: High expression of NGAL in the kidney is associated with diabetic kidney injury in STZ rats, suggesting NCAL may play a role in tubular injury of DN. (C) 2015 Published by Elsevier Urban & Partner Sp. z o.o. on behalf of Medical University of Bialystok.