Neutrophil gelatinase-associated lipocalin (NGAL) is localised to the primary cilium in renal tubular epithelial cells - A novel source of urinary biomarkers of renal injury

Abstract Background Exposure to airborne fine particulate matter (PM2.5) has been declared to be harmful to the human kidney. However, whether activation of the autophagic pathway plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of kidney damage after PM2.5 exposure in vivo and in vitro. Results In the present study, statistically significant alterations in water intake, urine flow rate and mean blood pressure were observed between the PM2.5 group and FA group during the period of PM2.5 exposure. Exposed animals showed severe edema of renal tubular epithelial cells, capillary congestion, reduction of the glomerular urinary space and early pro-fibrotic state. Moreover, significant increases in the levels of early kidney damage markers were observed in the exposed rats and these animals exhibited more apoptosis rate in kidney cells. In addition, PM2.5 exposure resulted in the activation of the autophagic pathway, as evidenced by LC3-I to LC3-II conversion, P62 and beclin-1 activated. All of these effects are in concurrence with the presence of more autophagosomes both in vivo and in vitro after PM2.5 exposure. Conclusions Taken together, our findings indicated that PM2.5-induced renal injury via the activation of the autophagic pathway in renal tubular epithelial cells.

Download Full-text

DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury

Clinical & Experimental Immunology ◽

10.1111/cei.13048 ◽

2017 ◽

Vol 191 (1) ◽

pp. 107-115 ◽

Cited By ~ 12

Author(s):

D. Feng ◽

Y. Wang ◽

Y. Liu ◽

L. Wu ◽

X. Li ◽

...

Keyword(s):

Epithelial Cells ◽

Renal Injury ◽

Inflammatory Cytokine ◽

Cytokine Expression ◽

Tubular Epithelial Cells ◽

Acute Renal Injury ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular

Download Full-text

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

BMC Nephrology ◽

10.1186/s12882-021-02396-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Huayu Yang ◽

Haiping Chen ◽

Fenghua Liu ◽

Qing Ma

Keyword(s):

Diabetic Rats ◽

Diabetic Rat ◽

Tubular Epithelial Cells ◽

Tubular Injury ◽

Renal Tubular Epithelial Cells ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Matrix Metalloproteinases 9 ◽

Renal Tubular ◽

Neutrophil Gelatinase ◽

Diabetic Rat Model

Abstract 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.

Download Full-text