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

Kidney International
S JonesA O Phillips

Abstract

Proximal tubular cells (PTCs) contribute to pathological changes in the renal interstitium by the generation of cytokines and alterations in the composition of the extracellular matrix. Hyaluronan (HA) is a ubiquitous connective tissue polysaccharide that regulates cell function and tissue remodeling. In the current study, we investigated the regulation of HA generation by PTCs. Primary cultures of human PTCs were grown to confluence and stimulated under serum-free conditions with either interleukin-1 (IL-1) or 25 mmol/L D-glucose. Alterations in HA generation were detected by enzyme-linked immunosorbent assay, and alterations in HA synthase gene expression were examined by reverse transcription-polymerase chain reaction. Subsequently, the mechanisms of IL-1 beta and glucose-induced alterations in HA were examined utilizing HK-2 cells. Stimulation of human PTCs (HPTCs) with either IL-1 beta or 25 mmol/L D-glucose led to a significant increase in the HA concentration in the culture supernatant. In contrast, stimulation of HPTCs with transforming growth factor-beta1, basic fibroblast growth factor, or platelet-derived growth factor-AB did not stimulate HA production. The addition of IL-1 beta or 25 mmol/L D-glucose also increased...Continue Reading

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Citations

Nov 13, 2003·Current Diabetes Reports·Aled O Phillips
Aug 28, 2004·The American Journal of Pathology·Xiao Liang ZhangAled Phillips
Jun 12, 2003·The International Journal of Biochemistry & Cell Biology·Stuart George JonesAled Owain Phillips
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