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

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.

scholarly journals Caspase-11 promotes cisplatin-induced renal tubular apoptosis through a caspase-3-dependent pathway

2018 ◽  
Vol 314 (2) ◽  
pp. F269-F279 ◽  
Author(s):  
Naijun Miao ◽  
Bao Wang ◽  
Dan Xu ◽  
Yanzhe Wang ◽  
Xinxin Gan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Tubular Epithelial Cells ◽  
Tubular Injury ◽  
Renal Tubular Epithelial Cells ◽  
Small Interference Rna ◽  
Fluorescence Confocal Microscopy ◽  
Renal Tubular ◽  
Interference Rna

Renal tubular injury is the hallmark of cisplatin-induced nephrotoxicity. Caspase-11, a member of the caspase family, plays an important role in inflammation and cell death. However, its role in cisplatin-induced renal tubular injury remains unclear. In cisplatin-treated mice, caspase-11 expression was significantly elevated and the expression of caspase-11 was mainly located in renal tubule. Inhibition of caspase-11 by small-interference RNA or its inhibitor wedelolactone attenuated cisplatin-induced renal dysfunction and tubular injury. In cultured primary renal tubular epithelial cells, cisplatin significantly promoted the expression and activation of caspase-11. Inhibition of caspase-11 by small-interference RNA reduced cisplatin-induced cell apoptosis. Overexpression of caspase-11 promoted cell apoptosis by activating the caspase-3-related cell apoptosis. Furthermore, coimmunoprecipitation results showed there was a direct interaction between caspase-11 and caspase-3, and the interaction was enhanced by cisplatin. The fluorescence confocal microscopy results showed that caspase-11 and caspase-3 were colocalized in the cytoplasm of renal tubular epithelial cells. These results demonstrate that caspase-11 plays an important role in cisplatin-induced renal tubular injury. Caspase-11 promotes renal epithelial cell apoptosis by activating the caspase-3-dependent apoptotic pathway. Caspase-11 might be a potential target for therapeutic treatment against cisplatin-induced nephrotoxicity.

Evaluation of renal injury in children with uncorrected CHDs with significant shunt using urinary neutrophil gelatinase-associated lipocalin

2020 ◽  
Vol 30 (9) ◽  
pp. 1313-1320
Author(s):  
Promise Monday ◽  
Nosakhare J. Idouriyekemwen ◽  
Wilson E. Sadoh
Keyword(s):  
Renal Injury ◽  
Tertiary Hospital ◽  
Renal Ultrasound ◽  
Healthy Children ◽  
Ultrasound Scan ◽  
Tubular Injury ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Cardiology Clinic ◽  
Renal Tubular ◽  
Neutrophil Gelatinase

AbstractBackground:CHDs can be complicated by renal injury which worsens morbidity and mortality. Urinary neutrophil gelatinase-associated lipocalin, a sensitive and specific biomarker of renal tubular injury, has not been studied in children with uncorrected CHDs. This study evaluated renal injury in children with uncorrected CHDs using this biomarker.Methods:The patients were children with uncorrected CHDs with significant shunt confirmed on echocardiogram with normal renal ultrasound scan, in the paediatric cardiology clinic of a tertiary hospital. The controls were age-matched healthy children recruited from general practice clinics. Information on bio-data and socio-demographics were collected and urine was obtained for measurement of urinary neutrophil gelatinase-associated lipocalin levels.Results:A total of 65 children with uncorrected CHDs aged 2 to 204 months were recruited. Thirty-one (47.7%) were males while 36 (55.4%) had acyanotic CHDs. The median urinary neutrophil gelatinase-associated lipocalin level of patients of 26.10 ng/ml was significantly higher than controls of 16.90 ng/ml (U = 1624.50, p = 0.023). The median urinary neutrophil gelatinase-associated lipocalin level of patients with cyanotic and acyanotic CHDs were 30.2 ng/ml and 22.60 ng/ml respectively; (Mann–Whitney U = 368.50, p = 0.116). The prevalence of renal injury using 95th percentile cut-off value of urinary neutrophil gelatinase-associated lipocalin was 16.9%. Median age of patients with renalinjury was 16 (4–44) months.Conclusions:Children with uncorrected CHDs have renal injury detected as early as infancy. The use of urinary neutrophil gelatinase-associated lipocalin in early detection of renal injury in these children may enhance early intervention and resultant prevention of morbidity and reduction in mortality.

scholarly journals Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats

2014 ◽  
Vol 2 (4) ◽  
pp. 490-494 ◽  
Author(s):  
TAO PENG ◽  
JIE WANG ◽  
JUNHUI ZHEN ◽  
ZHAO HU ◽  
XIANGDONG YANG
Keyword(s):  
Epithelial Cells ◽  
Diabetic Rats ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular

Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Reversible versus Persistent Renal Tubular Damage in ST-Segment Myocardial Infarction Patients

2021 ◽  
Vol 50 (6) ◽  
pp. 925-930
Author(s):  
Ariel Banai ◽  
Keren-Lee Rozenfeld ◽  
Itamar Loewenstein ◽  
David Zahler ◽  
Moshe Shtark ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Kidney Injury ◽  
Coronary Intervention ◽  
Tubular Damage ◽  
Symptom Duration ◽  
Tubular Injury ◽  
Renal Tubular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Renal Tubular ◽  
Neutrophil Gelatinase

<b><i>Background:</i></b> Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients. <b><i>Methods:</i></b> Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL &#x3c;100 ng/mL in both exams), reversible tubular damage (NGAL &#x3e;100 ng/mL at 0 h but &#x3c;100 ng/mL at 24 h), and persistent tubular damage (NGAL &#x3e;100 ng/mL at both 0 and 24 h). <b><i>Results:</i></b> Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.04; <i>p</i> = 0.04) and for symptom duration &#x3e;360 min (OR 2.66, 95% CI 1.07–6.63; <i>p</i> = 0.03). <b><i>Conclusions:</i></b> Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions.

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