scholarly journals Blockade of prostaglandin E2 receptor 4 ameliorates nephrotoxic serum nephritis

2018 ◽  
Vol 315 (6) ◽  
pp. F1869-F1880 ◽  
Author(s):  
Ida Aringer ◽  
Katharina Artinger ◽  
Alexander H. Kirsch ◽  
Corinna Schabhüttl ◽  
Katharina Jandl ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Neutrophil Infiltration ◽  
Prostaglandin E ◽  
Tubular Epithelial Cells ◽  
Tubular Cells ◽  
Nephrotoxic Serum Nephritis ◽  
Immune Mediated ◽  
Disease Initiation ◽  
Prostaglandin E2 Receptor

Prostaglandin E2 (PGE2) signaling is known to modulate inflammation and vascular resistance. Receptors of PGE2 [E-type prostanoid receptors (EP)] might be an attractive pharmacological target in immune-mediated diseases such as glomerulonephritis. We hypothesized that selective EP4 antagonism improves nephrotoxic serum nephritis (NTS) by its anti-inflammatory properties. Mice were subjected to NTS and treated with the EP4 antagonist ONO AE3-208 (10 mg·kg body wt−1·day−1] or vehicle starting from disease initiation. In one set of experiments, treatment was started 4 days after NTS induction. Tubular epithelial cells were evaluated in vitro under starving conditions. EP4 antagonist treatment significantly improved the NTS phenotype without affecting blood pressure levels. Remarkably, the improved NTS phenotype was also observed when treatment was started 4 days after NTS induction. EP4 antagonism decreased tubular chemokine (C-X-C motif) ligand ( Cxcl) 1 and Cxcl-5 expression and thereby subsequently reduced interstitial neutrophil infiltration into the kidney. In vitro, tubular epithelial cells increasingly expressed Cxcl-5 mRNA and Cxcl-5 protein when treated with PGE2 or an EP4 agonist under starving conditions, which was blunted by EP4 antagonist treatment. Together, EP4 antagonism improves the NTS phenotype, probably by decreasing mainly Cxcl-5 production in tubular cells, thereby reducing renal neutrophil infiltration.

Cross talk between primary human renal tubular cells and endothelial cells in cocultures

2012 ◽  
Vol 302 (8) ◽  
pp. F1055-F1062 ◽  
Author(s):  
Farah Tasnim ◽  
Daniele Zink
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Renal Disease ◽  
Cross Talk ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Tubular Cells ◽  
Renal Tubular

Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.

Inhibition of prostaglandin biosynthesis in renal (MDCK) cells by cAMP

1983 ◽  
Vol 245 (1) ◽  
pp. C163-C163 ◽  
Author(s):  
A. Hassid
Keyword(s):  
Epithelial Cells ◽  
Mdck Cells ◽  
Biological Properties ◽  
Prostaglandin E ◽  
Tubular Epithelial Cells ◽  
Prostaglandin Biosynthesis ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Arachidonate Metabolite ◽  
Renal Tubular

Page C369: A. Hassid. “Inhibition of prostaglandin biosynthesis in renal (MDCK) cells by cAMP.” Page C369: in the abstract, the first sentence should read: Cultured renal tubular cells (MDCK) have many of the biological properties of cortical medullary tubular epithelial cells, including the ability to synthesize prostaglandin E2 (PGE2) as the major arachidonate metabolite. Page C373: Table 3 should read as follows: (See PDF)

scholarly journals Erythropoietin expands a stromal cell population that can mediate renoprotection

2008 ◽  
Vol 295 (4) ◽  
pp. F1017-F1022 ◽  
Author(s):  
Baoyuan Bi ◽  
Jiankan Guo ◽  
Arnaud Marlier ◽  
Shin Ru Lin ◽  
Lloyd G. Cantley
Keyword(s):  
Epithelial Cells ◽  
Ischemia Reperfusion ◽  
Peripheral Circulation ◽  
Tubular Epithelial Cells ◽  
Tubular Injury ◽  
Tubular Cells ◽  
Toxic Injury ◽  
Proliferation In Vitro

Recent studies have demonstrated that erythropoietin (EPO) receptors are expressed on tubular epithelial cells and that EPO can protect tubular cells from injury in vitro and in vivo. Separate studies have demonstrated that marrow stromal cells (MSCs) exert a renoprotective effect in ischemia-reperfusion and cisplatin tubular injury via the secretion of factors that reduce apoptosis and increase proliferation of tubular epithelial cells. In the present study we demonstrate that MSCs express EPO receptors and that EPO can protect MSCs from serum deprivation-induced cell death and can stimulate MSC proliferation in vitro. The administration of EPO to mice resulted in the expansion of CD45-Flk1-CD105+ MSCs in the bone marrow and in the spleen and mobilized these cells as well as CD45-Flk1+ endothelial progenitor cells into the peripheral circulation. Consistent with previous reports, the administration of EPO diminished the decline in renal function associated with cisplatin administration. This effect was partially reproduced by intraperitoneal injection of cultured EPO-mobilized cells in cisplatin-treated mice. Thus the in vivo expansion and/or activation of these cells may contribute to the renoprotective effects of EPO to protect tubular cells from toxic injury.

scholarly journals Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1413
Author(s):  
Tjessa Bondue ◽  
Fanny O. Arcolino ◽  
Koenraad R. P. Veys ◽  
Oyindamola C. Adebayo ◽  
Elena Levtchenko ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Kidney Diseases ◽  
Cell Types ◽  
Cell Models ◽  
Tubular Epithelial Cells ◽  
Disease Mechanisms ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Disease Cell

Epithelial cells exfoliated in human urine can include cells anywhere from the urinary tract and kidneys; however, podocytes and proximal tubular epithelial cells (PTECs) are by far the most relevant cell types for the study of genetic kidney diseases. When maintained in vitro, they have been proven extremely valuable for discovering disease mechanisms and for the development of new therapies. Furthermore, cultured patient cells can individually represent their human sources and their specific variants for personalized medicine studies, which are recently gaining much interest. In this review, we summarize the methodology for establishing human podocyte and PTEC cell lines from urine and highlight their importance as kidney disease cell models. We explore the well-established and recent techniques of cell isolation, quantification, immortalization and characterization, and we describe their current and future applications.

scholarly journals Identification of a microRNA signature in renal fibrosis: role of miR-21

2011 ◽  
Vol 301 (4) ◽  
pp. F793-F801 ◽  
Author(s):  
Abolfazl Zarjou ◽  
Shanzhong Yang ◽  
Edward Abraham ◽  
Anupam Agarwal ◽  
Gang Liu
Keyword(s):  
Epithelial Cells ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Response To Treatment ◽  
Tubular Epithelial Cells ◽  
Altered Expression ◽  
Tnf Α ◽  
Tgf Β1

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis.

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