Evaluation of the Diagnostic Potential of uPAR as a Biomarker in Renal Biopsies of Patients with FSGS

Silva, Crislaine Aparecida da; Araújo, Liliane Silvano; Monteiro, Maria Luíza Gonçalves dos Reis; Pereira, Lívia Helena de Morais; Silva, Marcos Vinícius da; Castellano, Lúcio Roberto Cançado; Corrêa, Rosana Rosa Miranda; Reis, Marlene Antônia dos; Machado, Juliana Reis

doi:10.1155/2019/1070495

Cited by 7 publications

(11 citation statements)

References 32 publications

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“…The occurrence of FSGS is related to a variety of mechanisms. Podocyte injury is the central link of FSGS [16,17]. Glomerular sclerosis is the final pathological change in FSGS caused by the excessive accumulation of the glomerular extracellular matrix (ECM).…”

Section: Discussionmentioning

confidence: 99%

Anti-apoptosis mechanism of triptolide based on network pharmacology in focal segmental glomerulosclerosis rats

Jiang

Song

et al. 2020

Bioscience Reports

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Triptolide (TPL), the active component of Tripterygium wilfordii, exhibits anti-cancer and antioxidant functions. We aimed to explore the anti-apoptosis mechanism of TPL based on network pharmacology and in vivo and in vitro research validation using a rat model of focal segmental glomerulosclerosis (FSGS). The chemical structures and pharmacological activities of the compounds reported in T. wilfordii were determined and used to perform the network pharmacology analysis. The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was then used to identify the network targets for 16 compounds from Tripterygium wilfordii. Our results showed that 47 overlapping genes obtained from the GeneCards and OMIM databases were involved in the occurrence and development of FSGS and used to construct the protein–protein interaction (PPI) network using the STRING database. Hub genes were identified via the MCODE plug-in of the Cytoscape software. IL4 was the target gene of TPL in FSGS and was mainly enriched in the cell apoptosis term and p53 signaling pathway, according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. TPL inhibited FSGS-induced cell apoptosis in rats and regulated IL4, nephrin, podocin, and p53 protein levels via using CCK8, TUNEL, and Western blot assays. The effects of IL4 overexpression, including inhibition of cell viability and promotion of apoptosis, were reversed by TPL. TPL treatment increased the expression of nephrin and podocin and decreased p53 expression in rat podocytes. In conclusion, TPL inhibited podocyte apoptosis by targeting IL4 to alleviate kidney injury in FSGS rats.

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Section: Discussionmentioning

confidence: 99%

Anti-apoptosis mechanism of triptolide based on network pharmacology in focal segmental glomerulosclerosis rats

Jiang

Song

et al. 2020

Bioscience Reports

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“…The diagnosis of DN was performed with three samples used for light microscopy (LM), direct immunofluorescence (IF) and transmission electron microscopy (TEM) according to the standard procedures [18].…”

Section: Renal Histopathologymentioning

confidence: 99%

“…Ultra-thin sections of 60 nm were prepared and placed in nickel grids. Sections were then stained with uranyl acetate and examined under a transmission electron microscope (EM-900; Zeiss, Germany) [18]. TEM was used to measure thickness of the glomerular basement membrane (GBM) and to exclude or identify renal diseases overlapping DN.…”

Section: Renal Histopathologymentioning

confidence: 99%

Renal expression of cytokines and chemokines in diabetic nephropathy

et al. 2020

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Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, thus considered an inflammatory disease. However, further studies are required to assess the renal damage caused by the action of these molecules. Therefore, the objective of this study was to analyze the expression of cytokines and chemokines in renal biopsies from patients with DN and to correlate it with interstitial inflammation and decreased renal function. Methods: Forty-four native renal biopsies from patients with DN and 23 control cases were selected. In situ expression of eotaxin, MIP-1α (macrophage inflammatory protein-1α), IL-8 (interleukin-8), IL-4, IL-10, TNF-α (tumor necrosis factor-α), TNFR1 (tumor necrosis factor receptor-1), IL-1β, and IL-6 were evaluated by immunohistochemistry. Results: The DN group showed a significant increase in IL-6 (p < 0.0001), IL-1β (p < 0.0001), IL-4 (p < 0.0001) and eotaxin (p = 0.0012) expression, and a decrease in TNFR1 (p = 0.0107) and IL-8 (p = 0.0262) expression compared to the control group. However, there were no significant differences in IL-10 (p = 0.4951), TNF-α (p = 0.7534), and MIP-1α (p = 0.3816) expression among groups. Regarding interstitial inflammation, there was a significant increase in IL-6 in scores 0 and 1 compared to score 2 (p = 0.0035), in IL-10 in score 2 compared to score 0 (p = 0.0479), and in eotaxin in score 2 compared to scores 0 and 1 (p < 0.0001), whereas IL-8 (p = 0.0513) and MIP-1α (p = 0.1801) showed no significant differences. There was a tendency for negative correlation between eotaxin and estimated glomerular filtration rate (eGFR) (p = 0.0566). Conclusions: Our results indicated an increased in situ production of cytokines and chemokines in DN, including IL-6, IL-1β, IL-4, and eotaxin. It was observed that, possibly, eotaxin may have an important role in the progression of interstitial inflammation in DN and in eGFR decrease of these patients.

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“…Previous results from our group have shown that podocytes have increased expression of urokinase plasminogen activator receptor (uPAR) in situ in biopsies from adult [ 8 ] and pediatric [ 9 ] patients with morphological lesions compatible with FSGS. From these findings, we evaluated the possible causes of cellular injury in podocytopathies.…”

Section: Resultsmentioning

confidence: 99%

“…For TEM, the sample was fixed with Karnovsky 2.5% + ruthenium red 0.2% and post-fixed in osmium tetroxide 2%, then dehydrated in graded alcohols and acetone solutions and embedded in Epon 812 resin. Ultrathin 60-nm-thick sections were cut and placed onto nickel grids and were subsequently contrasted with lead citrate 1% and uranyl acetate 3% and examined under an EM-900 transmission electron microscope (Zeiss, Germany) [ 8 , 9 ].…”

Section: Methodsmentioning

confidence: 99%

In situ evaluation of podocytes in patients with focal segmental glomerulosclerosis and minimal change disease

et al. 2020

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Podocyte injury in focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) results from the imbalance between adaptive responses that maintain homeostasis and cellular dysfunction that can culminate in cell death. Therefore, an in situ analysis was performed to detect morphological changes related to cell death and autophagy in renal biopsies from adult patients with podocytopathies. Forty-nine renal biopsies from patients with FSGS (n = 22) and MCD (n = 27) were selected. In situ expression of Wilms Tumor 1 protein (WT1), light chain microtubule 1-associated protein (LC3) and caspase-3 protein were evaluated by immunohistochemistry. The foot process effacement and morphological alterations related to podocyte cell death and autophagy were analyzed with transmission electronic microscopy. Reduction in the density of WT1-labeled podocytes was observed for FSGS and MCD cases as compared to controls. Foot process width (FPW) in control group was lower than in cases of podocytopathies. In FSGS group, FPW was significantly higher than in MCD group and correlated with proteinuria. A density of LC3-labeled podocytes and the number of autophagosomes in podocytes/ pedicels were higher in the MCD group than in the FSGS group. The number of autophagosomes correlated positively with the estimated glomerular filtration rate in cases of MCD. The density of caspase-3-labeled podocytes in FSGS and MCD was higher than control group, and a higher number of podocytes with an evidence of necrosis was detected in FSGS cases than in MCD and control cases. Podocytes from patients diagnosed with FSGS showed more morphological and functional alterations resulting from a larger number of lesions and reduced cell adaptation.

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Evaluation of the Diagnostic Potential of uPAR as a Biomarker in Renal Biopsies of Patients with FSGS

Cited by 7 publications

References 32 publications

Anti-apoptosis mechanism of triptolide based on network pharmacology in focal segmental glomerulosclerosis rats

Anti-apoptosis mechanism of triptolide based on network pharmacology in focal segmental glomerulosclerosis rats

Renal expression of cytokines and chemokines in diabetic nephropathy

In situ evaluation of podocytes in patients with focal segmental glomerulosclerosis and minimal change disease

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