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Regulation of hyaluronan-stimulated VCAM-1 expression in murine renal tubular epithelial cells


Schawalder, Aaron; Oertli, Beat; Beck-Schimmer, Beatrice; Wüthrich, Rudolf P (1999). Regulation of hyaluronan-stimulated VCAM-1 expression in murine renal tubular epithelial cells. Nephrology, Dialysis, Transplantation, 14(9):2130-2136.

Abstract

Background. Cytokines stimulate the expression of the adhesion molecule VCAM-1 in renal tubular epithelial cells. We have recently shown that VCAM-1 can also be upregulated by low molecular weight breakdown products of the matrix constituent hyaluronan (HA) (J Immunol 1998; 161: 3431-3437). The mechanisms of VCAM-1 expression in response to HA remain to be defined. Methods. Using a defined mouse cortical tubular (MCT) cell line we investigated the effect of protein kinase C (PKC) and tyrosine kinase (TK) inhibition on the HA-stimulated VCAM-1 expression by cell ELISA and RT-PCR or Northern blotting. Furthermore, we examined the effect of PKC and TK inhibition on NF-κB. Results. We found that the PKC inhibitor GF109203X (acting on conventional, novel and atypical isoforms) inhibited the HA-stimulated VCAM-1 expression in MCT cells dose-dependently up to 90%, whereas chelerythrine (acting on conventional and novel isoforms) had no effect. Downregulation of PKC with PMA did not prevent the HA-stimulated VCAM-1 expression, suggesting that Ca2+- and diacylglycerol-independent (atypical) isoforms of PKC are involved. The TK inhibitor genistein also inhibited the HA-stimulated VCAM-1 expression at the mRNA and protein level up to 70%. Interestingly, the HA-stimulated nuclear translocation of NF-κB could not be prevented with GF109203X and genistein. Conclusion. These data demonstrate that the HA-stimulated VCAM-1 expression in MCT cells involves PKC and TK pathways. The absence of an effect of PKC and TK inhibitors on the nuclear translocation of NF-κB suggests that additional transcription factors are involved for VCAM-1 expression

Abstract

Background. Cytokines stimulate the expression of the adhesion molecule VCAM-1 in renal tubular epithelial cells. We have recently shown that VCAM-1 can also be upregulated by low molecular weight breakdown products of the matrix constituent hyaluronan (HA) (J Immunol 1998; 161: 3431-3437). The mechanisms of VCAM-1 expression in response to HA remain to be defined. Methods. Using a defined mouse cortical tubular (MCT) cell line we investigated the effect of protein kinase C (PKC) and tyrosine kinase (TK) inhibition on the HA-stimulated VCAM-1 expression by cell ELISA and RT-PCR or Northern blotting. Furthermore, we examined the effect of PKC and TK inhibition on NF-κB. Results. We found that the PKC inhibitor GF109203X (acting on conventional, novel and atypical isoforms) inhibited the HA-stimulated VCAM-1 expression in MCT cells dose-dependently up to 90%, whereas chelerythrine (acting on conventional and novel isoforms) had no effect. Downregulation of PKC with PMA did not prevent the HA-stimulated VCAM-1 expression, suggesting that Ca2+- and diacylglycerol-independent (atypical) isoforms of PKC are involved. The TK inhibitor genistein also inhibited the HA-stimulated VCAM-1 expression at the mRNA and protein level up to 70%. Interestingly, the HA-stimulated nuclear translocation of NF-κB could not be prevented with GF109203X and genistein. Conclusion. These data demonstrate that the HA-stimulated VCAM-1 expression in MCT cells involves PKC and TK pathways. The absence of an effect of PKC and TK inhibitors on the nuclear translocation of NF-κB suggests that additional transcription factors are involved for VCAM-1 expression

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 September 1999
Deposited On:25 Sep 2018 14:21
Last Modified:04 Oct 2018 11:37
Publisher:Oxford University Press
ISSN:0931-0509
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/ndt/14.9.2130
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093ndt1492130 (Library Catalogue)

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