Up-regulation of matrix metalloproteinases-9 in the kidneys of diabetic rats and the association with neutrophil gelatinase-associated lipocalin.

Published on Jun 3, 2021in BMC Nephrology1.913
· DOI :10.1186/S12882-021-02396-W
Huayu Yang2
Estimated H-index: 2
(Capital Medical University),
Haiping Chen3
Estimated H-index: 3
(Capital Medical University)
+ 1 AuthorsQing Ma5
Estimated H-index: 5
(Capital Medical University)
BACKGROUND Matrix metalloproteinases-9 (MMP-9) can regulate extracellular matrix deposition in diabetic glomerular injury. However, it remains unknown whether MMP-9 is involved in the renal tubular injury. Meanwhile, neutrophil gelatinase-associated lipocalin (NGAL), defined as a biomarker of proximal tubular injury, may influence MMP-9 by forming the MMP-9/NGAL complex. The aim of this study was to investigate MMP-9 expression in proximal renal tubules and the relationship of MMP-9 and NGAL in diabetic rat model treated with Valsartan. METHODS Sprague Dawley rats were randomly divided into three groups: Diabetic group, Control group, and Treated group. The diabetic rat model was established by injection of streptozotocin. Related indexes were measured at the end of the 2nd, 4th, 8th and 12th week post-modeling. RESULTS In diabetic groups, the concentrations of MMP-9 markedly increased in the serum and urine of rats in the early stage, even before the appearance of pathological albuminuria. Markedly elevated MMP-9/NGAL complex concentrations were also tested in diabetic groups. Western blot and qPCR tests confirmed that MMP-9 expression levels in the proximal renal tubular epithelial cells of diabetic rats were significantly higher than in control groups (P < 0.05). Correlation analysis showed that MMP-9 was positively correlated with NGAL at both protein and gene expression levels. In addition, Valsartan observably reduced tubular injury as well as MMP-9 expression in diabetic rats. CONCLUSIONS In diabetic kidney injury, the expression of MMP-9 in the proximal renal tubular epithelial cells was significantly increased. Besides, a positive correlation was found between MMP-9 and NGAL expression, along with high levels of MMP-9/NGAL complex, which indicated that NGAL might participate in the regulation of MMP-9 expression. The administration of Valsartan may reduce this effect.
#1Estrellita UijlH-Index: 7
#2Daan C 't Hart (Radboud University Nijmegen)H-Index: 1
Last. Alexander H. J. DanserH-Index: 29
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#1Samy Makary (Suez Canal University)H-Index: 8
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This study examined the effect of the aromatase inhibitor letrozole (0.5 mg/kg) alone or in combination with the angiotensin-receptor blocker valsartan (30 mg/kg) against streptozocin-induced diabe...
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Introduction. This study was aimed to investigate the efficacy of matrix metalloproteinase - 9 ( MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the neutrophil gelatinase-associated lipocalin (NGAL)-bound form of MMP-9 (MMP-9/NGAL complex) markers in the determination of early nephropathy in patients with type 2 diabetes mellitus. Materials and Methods. Twenty-five type 2 diabetic patients with normoalbuminuria, 27 type 2 diabetic patients with microalbuminuria, and 23 healthy cont...
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#1Li Ling (Guangdong Medical College)H-Index: 2
#2Libo Chen (Guangdong Medical College)H-Index: 2
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Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-r...
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#1Yamini B. TripathiH-Index: 26
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#1Fenghua Liu (Capital Medical University)H-Index: 1
#2Huayu Yang (Capital Medical University)H-Index: 2
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Abstract 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 diab...
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