PMID: 15331401Aug 28, 2004Paper

Renal proximal tubular epithelial cell transforming growth factor-beta1 generation and monocyte binding

The American Journal of Pathology
Xiao-Liang ZhangAled O Phillips

Abstract

With increasing awareness of the importance of renal cortical interstitial fibrosis, interest has focused on the mechanisms that stimulate generation of profibrotic factors including transforming growth factor (TGF)-beta1, by resident cells, such as proximal tubular epithelial cells (PTCs). Infiltration of monocytes, has been implicated in the pathogenesis of a wide variety of renal diseases, however, how interaction between monocytes and PTCs may affect the generation of TGF-beta1 by the resident cell is unknown. We demonstrate that monocytes stimulate TGF-beta1 transcription and protein synthesis by PTCs. This was dependent on direct cell contact and TGF-beta1 transcriptional activation that was dependent on ICAM-1 binding of unstimulated monocytes. This was mimicked by antibody cross-linking of PTC surface ICAM-1. We have previously identified hyaluronan (HA)-based structures on the surface of PTCs, both primary cultures and the HK-2 cell line. Removal of cell-surface HA increased ICAM-1-dependent monocyte binding and stimulation of TGF-beta1 synthesis. Furthermore, we demonstrate that binding of monocytes to HA-based structures on the cell surface of HK-2 cells interferes with this response. In summary, we have demonstrated...Continue Reading

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Citations

Dec 15, 2006·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Xueguang ZhangZhong Yin
Oct 3, 2008·American Journal of Physiology. Renal Physiology·Makoto HagiwaraJulie Chao
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May 12, 2006·Journal of the American Society of Nephrology : JASN·Wisam SelbiAled O Phillips
Apr 29, 2005·Journal of the American Society of Nephrology : JASN·Fiona Y ChowGregory H Tesch
Dec 3, 2004·Journal of the American Society of Nephrology : JASN·Xiao Liang ZhangAled O Phillips
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