Regulation of renal proximal tubular epithelial cell hyaluronan generation: Implications for diabetic nephropathy

Jones, Stuart; Jones, Suzanne; Phillips, Aled Owain

doi:10.1046/j.1523-1755.2001.0590051739.x

Cited by 89 publications

(72 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, exposure to high glucose concentrations also increases hyaluronan synthesis in renal proximal tubular cells (15), in renal interstitial fibroblasts (16), and in vascular smooth muscle cells (17). Thus, the broader implications of this model for diabetic pathology become clearer.…”

Section: Figmentioning

confidence: 94%

“…Previous studies have shown increased hyaluronan content in glomeruli isolated from diabetic animals (13) and in mesangial cells cultured in medium with a high glucose concentration (14). Exposure to high glucose concentrations also increases hyaluronan synthesis in renal proximal tubular cells (15), in renal interstitial fibroblasts (16), and in vascular smooth muscle cells (17), all of which are involved in normal kidney physiology.…”

mentioning

confidence: 94%

See 1 more Smart Citation

Hyaluronan Structures Synthesized by Rat Mesangial Cells in Response to Hyperglycemia Induce Monocyte Adhesion

Ai-min

Hascall

2004

Journal of Biological Chemistry

128

View full text Add to dashboard Cite

Mesangial expansion, the principal glomerular lesion in diabetic nephropathy, is preceded by a phenotypic activation and transient proliferation of the glomerular mesangial cells and by a prominent glomerular infiltration of monocytes and macrophages. Because this infiltration seems to play a key role in the subsequent mesangial matrix expansion, we tested the response of cultures of rat mesangial cells (RMCs) for monocyte adhesion in response to hyperglycemia. Increasing the medium glucose concentration from 5.6 mM (normal) to 25.6 mM (hyperglycemic) significantly increased hyaluronan in the cell matrix, with a concurrent 3-to 4-fold increase in adhesion of U937 monocytic leukemic cells to cultures of near confluent RMCs. These responses were attributed directly to the high glucose concentration and not to increased extracellular osmolality. The monocytes primarily bind directly to hyaluronan-based structures in vitro. Abnormal deposits of hyaluronan were found in glomeruli of kidney sections from diabetic rats 1 week after streptozotocin treatment, often with closely associated monocytes/macrophages, suggesting that similar structures are relevant in vivo. The monocyte adhesion response to high glucose concentration required growth stimulation of RMCs by serum and activation of protein kinase C, and was inhibited by prior passage of the RMCs in the presence of heparin. These results suggest that the response may be cell growth state and protein kinase C-dependent. When incubated with the viral mimetic, poly I:C, in the presence of normal glucose, heparin-passaged RMCs still increased cell-associated hyaluronan and exhibited hyaluronan-mediated adhesion of monocytes, indicating that the two stimuli, high glucose and viral mimetic, induce the production of the hyaluronan structures that promote monocyte adhesion by distinctly different intracellular signaling mechanisms.Mesangial expansion, the principal glomerular lesion in diabetic nephropathy, reduces the area for filtration and leads eventually to sclerosis and renal failure (1, 2). However, the expansion of the mesangial extracellular matrix (ECM) 1 and the sclerosis that characterize diabetic nephropathy are preceded by a phenotypic activation and transient proliferation of the glomerular mesangial cells. This is followed by a prominent glomerular infiltration of monocytes and macrophages (3-5) that seems to play a key role in the subsequent mesangial matrix expansion, hypercellularity, and onset of proteinuria (6, 7). Nevertheless, the molecular mechanisms underlying glomerular infiltration by monocytes and macrophages are still unclear.The interaction of monocytes with mesangial cells in culture has been studied previously using U937 cells, a monocytic leukemic cell line that is a widely accepted model for monocyte adhesion (7,8), and mesangial cell cultures incubated in media with high glucose concentrations bind more U937 cells (7). Generally, the interactions between monocytes and resident cells involve: (i) monocyte cell surface proteins, including C...

show abstract

Section: Figmentioning

confidence: 94%

mentioning

confidence: 94%

Hyaluronan Structures Synthesized by Rat Mesangial Cells in Response to Hyperglycemia Induce Monocyte Adhesion

Ai-min

Hascall

2004

Journal of Biological Chemistry

128

View full text Add to dashboard Cite

show abstract

“…We have previously demonstrated that IL-1␤ is a potent stimulus for HA synthesis as assessed by quantitation of HA in the cell culture supernatant of IL-1␤-treated PTC (10). We therefore sought to determine the effect of IL-1␤ on HA cable formation and monocyte binding in HK2 cells.…”

Section: Il-1␤ Induced Ha Synthesis But Does Not Increase Ha Cable Fomentioning

confidence: 99%

“…We recently examined the regulation of HA synthesis by renal PTC in vitro under conditions that mimic the diabetic state (10). These studies demonstrate that exposure of PTC to elevated D-glucose concentrations leads to nuclear factor-B (NF-B)-dependent transcriptional activation of the HA synthase HAS2 and stimulation of HA synthesis.…”

mentioning

confidence: 99%

BMP-7 Modulates Hyaluronan-Mediated Proximal Tubular Cell-Monocyte Interaction

Selbi¹,

Motte²,

Hascall³

et al. 2004

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. Increased synthesis of hyaluronan (HA) in the renal corticointerstitium has been documented in renal injury, although the functional significance of this is unclear. The aim of the work presented in the current study was to examine the role of HA in monocyte binding by proximal tubular cells (PTC). Using the PTC line HK-2, the authors show that unstimulated cells formed pericellular HA cable-like structures that bound mononuclear leukocytes via their cell surface CD44. Stimulation with bone morphogenic protein-7 (BMP-7) led to increased formation of HA cable-like structures and also a dosedependent increase in CD44-dependent binding of radiolabeled

show abstract

“…End stage renal failure is most frequently characterized by progressive interstitial fibrosis and tubular atrophy (10), and increased expression of HA in the renal corticointerstitium is associated with this progression (11,12). In high glucose concentrations, which mimic diabetic nephropathy, renal proximal tubular epithelial cells synthesize high levels of HA, which is coincident with specific up-regulation of transcription at the HAS2 locus (13). The mesothelial cells that line the peritoneal membrane synthesize HA as a normal constituent of human peritoneal effluent, and this synthesis is up-regulated during periods of peritonitis in patients undergoing peritoneal dialysis (14).…”

mentioning

confidence: 99%

Identification and Analysis of the Promoter Region of the Human Hyaluronan Synthase 2 Gene

Monslow

Williams

Guy

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hyaluronan (HA) is a linear glycosaminoglycan of the vertebrate extracellular matrix that is synthesized at the plasma membrane by the HA synthase (HAS) enzymes HAS1, -2 and -3. The regulation of HA synthesis has been implicated in a variety of extracellular matrixmediated and pathological processes, including renal fibrosis. We have recently described the genomic structures of each of the human HAS genes. In the present study, we analyzed the HAS2 promoter region. In 5 -rapid amplification of cDNA ends analysis of purified mRNA from human renal epithelial proximal tubular cells, we detected an extended sequence for HAS2 exon 1, relocating the transcription initiation site 130 nucleotides upstream of the reference HAS2 mRNA sequence, GenBank TM accession number NM_005328. A luciferase reporter gene assay of nested fragments spanning the 5 terminus of NM_005328 demonstrated the constitutive promoter activity of sequences directly upstream of the repositioned transcription initiation site but not of the newly designated exonic nucleotides. Using reverse transcription-PCR, expression of this extended HAS2 mRNA was demonstrated in a variety of human cell types, and orthologous sequences were detected in mouse and rat kidney. Alignment of human, murine, and equine genomic DNA sequences upstream of the repositioned HAS2 exon 1 provided evidence for the evolutionary conservation of specific transcription factor binding sites. The location of the HAS2 promoter will facilitate analysis of the transcriptional regulation of this gene in a variety of pathological contexts as well as in developmental models in which HAS2 null animals have an embryonic lethal phenotype.

show abstract

Regulation of renal proximal tubular epithelial cell hyaluronan generation: Implications for diabetic nephropathy

Abstract: This study demonstrates, to our knowledge for the first time, that increased HA synthesis in response to either IL-1 beta or elevated 25 mmol/L D-glucose is associated with NF-kappa B-activated transcription of HAS2.

Cited by 89 publications

References 35 publications

Hyaluronan Structures Synthesized by Rat Mesangial Cells in Response to Hyperglycemia Induce Monocyte Adhesion

Hyaluronan Structures Synthesized by Rat Mesangial Cells in Response to Hyperglycemia Induce Monocyte Adhesion

BMP-7 Modulates Hyaluronan-Mediated Proximal Tubular Cell-Monocyte Interaction

Identification and Analysis of the Promoter Region of the Human Hyaluronan Synthase 2 Gene

Contact Info

Product

Resources

About