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.

scholarly journals SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells

2020 ◽  
Vol 295 (48) ◽  
pp. 16328-16341
Author(s):  
Ji Young Kim ◽  
Yuntao Bai ◽  
Laura A. Jayne ◽  
Ferdos Abdulkader ◽  
Megha Gandhi ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Gene Ablation ◽  
Renal Tubular ◽  
Inducible Gene

Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, and cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxia, cytotoxicity, and inflammatory insults to renal tubular epithelial cells (RTECs), resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI. We find that Vgf nerve growth factor inducible gene up-regulation is a common transcriptional stress response in RTECs to ischemia-, cisplatin-, and rhabdomyolysis-associated renal injury. The Vgf gene encodes a secretory peptide precursor protein that has critical neuroendocrine functions; however, its role in the kidneys remains unknown. Our functional studies show that RTEC-specific Vgf gene ablation exacerbates ischemia-, cisplatin-, and rhabdomyolysis-associated AKI in vivo and cisplatin-induced RTEC cell death in vitro. Importantly, aggravation of cisplatin-induced renal injury caused by Vgf gene ablation is partly reversed by TLQP-21, a Vgf-derived peptide. Finally, in vitro and in vivo mechanistic studies showed that injury-induced Vgf up-regulation in RTECs is driven by the transcriptional regulator Sox9. These findings reveal a crucial downstream target of the Sox9-directed transcriptional program and identify Vgf as a stress-responsive protective gene in kidney tubular epithelial cells.

Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome

2006 ◽  
Vol 290 (1) ◽  
pp. R105-R113 ◽  
Author(s):  
Patricio E. Ray ◽  
Elena Tassi ◽  
Xue-Hui Liu ◽  
Anton Wellstein
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Renal Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Uremic Syndrome ◽  
Renal Tubular

A characteristic finding of childhood HIV-associated hemolytic uremic syndrome (HIV-HUS) is the presence of endothelial injury and microcystic tubular dilation, leading to a rapid progression of the renal disease. We have previously shown that a secreted fibroblast growth factor-binding protein (FGF-BP) is upregulated in kidneys from children affected with HIV-HUS and HIV nephropathy. Here, we sought to determine the potential role of FGF-BP in the pathogenesis of HIV-HUS. By immunohistochemical and in situ hybridization studies, we observed FGF-BP protein and mRNA upregulation in regenerating renal tubular epithelial cells from kidneys of HIV-Tg26 mice with late-stage renal disease, that is, associated with the development of microcystic tubular dilatation and accumulation of FGF-2. Moreover, FGF-BP increased the FGF-2-dependent growth and survival of cultured primary human renal glomerular endothelial cells and enhanced FGF-2-induced MAPK/ERK2 activation, as well as the proliferation of immortalized GM7373 endothelial cells. We propose that HIV-Tg26 mice are a clinically relevant model system to study the role of FGF-BP in the pathogenesis of HIV-associated renal diseases. Furthermore, the upregulation of FGF-BP by regenerating renal tubular epithelial cells may provide a mechanism by which the regenerative and angiogenic activity of FGF-2 in renal capillaries can be modulated in children with HIV-HUS and other renal disease.

Potential autocrine and paracrine mechanisms of recovery from mechanical injury of renal tubular epithelial cells

1998 ◽  
Vol 274 (3) ◽  
pp. F463-F472 ◽  
Author(s):  
Robert J. Anderson ◽  
Carla J. Ray
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Mechanical Injury ◽  
Renal Tubular Cell ◽  
Thymidine Uptake ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
The Media ◽  
Renal Tubular

The present studies were done to clarify potential pathways of the nephrogenic repair process. Media removed from mechanically injured vascular smooth muscle cells and LLC-PK1 renal tubular epithelial cells significantly stimulated[Formula: see text]thymidine uptake and cell number in quiescent LLC-PK1 cells, demonstrating the existence of potential autocrine and paracrine pathways of nephrogenic repair. The effect of mechanical injury resulting in release of one or more growth factors into culture media was also found in the opossum kidney OK renal tubular cell line. The nonspecific peptide growth factor antagonist suramin inhibited the effect of media from injured LLC-PK1 cells to stimulate[Formula: see text]thymidine uptake in quiescent LLC-PK1 cells. Exposure of quiescent LLC-PK1 cells to six growth factors, including acidic and basic fibroblastic growth factors (aFGF and bFGF), platelet-derived growth factors AA and BB (PDGF-AA and PDGF-BB), endothelin-2, and hepatocyte growth factor, reproduced the biological responses seen when quiescent LLC-PK1 cells were exposed to media from injured cells. Immunoblotting and enzyme-linked immunosorbent assay experiments demonstrated the presence of aFGF, bFGF, and PDGF-BB but not other candidate growth factors in the media from injured LLC-PK1 cells. A neutralizing antibody directed against bFGF attenuated the effect of media from injured cells to stimulate[Formula: see text]thymidine uptake in serum-starved LLC-PK1 cells. These results demonstrate that mechanical injury to renal tubular epithelial cells results in release of aFGF, bFGF, and PDGF-BB into the media and suggests that bFGF may be involved in an autocrine fashion to promote recovery from injury.

scholarly journals JAK2/Y343/STAT5 signaling axis is required for erythropoietin-mediated protection against ischemic injury in primary renal tubular epithelial cells

2008 ◽  
Vol 295 (6) ◽  
pp. F1689-F1695 ◽  
Author(s):  
A. C. Breggia ◽  
D. M. Wojchowski ◽  
J. Himmelfarb
Keyword(s):  
Epithelial Cells ◽  
Tissue Injury ◽  
Ischemic Injury ◽  
Erythropoietin Receptor ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Primary Mouse ◽  
Signaling Axis ◽  
Renal Tubular

Erythropoietin has emerged as a potential therapy for the treatment of ischemic tissue injury. In erythroid cells, the JAK2/Y343/STAT5 signaling axis has been shown to be necessary for stress but not steady-state erythropoiesis. The requirement for STAT5 activation in erythropoietin-mediated protection from ischemic injury has not been well-studied. To answer this question, we induced reproducible necrotic ischemic injury in primary mouse renal tubular epithelial cells (RTEC) in vitro. Using RTEC from erythropoietin receptor mutant mice with differential STAT5 signaling capabilities, we demonstrated first, that EPO administration either before or during injury significantly protects against mild-moderate but not severe necrotic cell death; and second, the JAK2/Y343/STAT5 signaling axis is required for protection against ischemic injury in primary mouse RTEC. In addition, we identified Pim-3, a prosurvival STAT5 target gene, as responsive to EPO in the noninjured kidney both in vitro and in vivo.

scholarly journals Klotho is regulated by transcription factor Sp1 in renal tubular epithelial cells

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Li ◽  
Yong Liu ◽  
Kailong Wang ◽  
Yinghui Huang ◽  
Wenhao Han ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Epithelial Cells ◽  
Renal Disease ◽  
Luciferase Reporter ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Transcription Factor Sp1 ◽  
Renal Tubular ◽  
Tgf Β1

Abstract Background Klotho is a multifunctional protein, which exists both in a membrane bound and a soluble form. In renal tubules, Klotho is involved in cell senescence, anti-oxidant response, and renal fibrosis, thus regulation of its expression is critical to understand its roles in renal diseases. Indeed, reduced expression was observed in various renal disease. However, the mechanisms underlying transcriptional regulation of the human klotho gene (KL) largely remain unknown. Results Here we demonstrated that the Klotho expression in human renal tubular epithelial cells (RTECs) was enhanced by overexpression of the transcription factor Sp1. On the contrary, Klotho expression was decreased by Sp1 knockdown. Besides, increased expression of Sp1 alleviated TGF-β1-induced fibrosis in HK-2 cells by inducing Klotho expression. Luciferase reporter assays and chromatin immunoprecipitation assays further identified the binding site of Sp1 was located in − 394 to − 289 nt of the KL promoter, which was further confirmed by mutation analysis. Conclusions These data demonstrate that KL is a transcriptional target of Sp1 and TGF-β1-induced fibrosis was alleviated by Sp1 in human RTECs by directly modulating Klotho expression, which help to further understand the transcriptional regulation of Klotho in renal disease models.

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