Effects of chemokines on proliferation and apoptosis of human mesangial cells.

Markus Wörnle,Monika Merkle,Holger Schmid,Bernhard Banas

doi:10.1186/1471-2369-5-8

Markus Wörnle, Monika Merkle + Show 2 more

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https://doi.org/10.1186/1471-2369-5-8

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Journal: BMC Nephrology	Publication Date: Jul 20, 2004
Citations: 76	License type: cc-by

Affiliation: Ludwig-Maximilians-Universität München

Abstract

BackgroundProliferation and apoptosis of mesangial cells (MC) are important mechanisms during nephrogenesis, for the maintenance of glomerular homeostasis as well as in renal disease and glomerular regeneration. Expression of chemokines and chemokine receptors by intrinsic renal cells, e.g. SLC/CCL21 on podocytes and CCR7 on MC is suggested to play a pivotal role during these processes. Therefore the effect of selected chemokines on MC proliferation and apoptosis was studied.MethodsProliferation assays, cell death assays including cell cycle analysis, hoechst stain and measurement of caspase-3 activity were performed.ResultsA dose-dependent, mesangioproliferative effect of the chemokine SLC/CCL21, which is constitutively expressed on human podocytes was seen via activation of the chemokine receptor CCR7, which is constitutively expressed on MC. In addition, in cultured MC SLC/CCL21 had a protective effect on cell survival in Fas-mediated apoptosis. The CXCR3 ligands IP-10/CXCL10 and Mig/CXCL9 revealed a proproliferative effect but did not influence apoptosis of MC. Both the CCR1 ligand RANTES/CCL5 and the amino-terminally modified RANTES analogue Met-RANTES which blocks CCR1 signalling had no effect on proliferation and apoptosis.ConclusionsThe different effects of chemokines and their respective receptors on proliferation and apoptosis of MC suggest highly regulated, novel biological functions of chemokine/chemokine receptor pairs in processes involved in renal inflammation, regeneration and glomerular homeostasis.

Highlights

Proliferation and apoptosis of mesangial cells (MC) are important mechanisms during nephrogenesis, for the maintenance of glomerular homeostasis as well as in renal disease and glomerular regeneration
Our group showed that SLC/CCL21 is constitutively expressed by glomerular podocytes and CCR7 constitutively expressed by MC [12]
We describe the different effects of the chemokines SLC/CCL21, IP-10/CXCL10, Mig/CXCL9, RANTES/CCL5 and the amino-terminally modified RANTES/CCL5 analogue Met-RANTES on mesangial cell proliferation and apoptosis, suggesting novel functions of chemokine/chemokine receptor pairs on local immunomodulation, glomerular regeneration and homeostasis

Summary

Introduction

Proliferation and apoptosis of mesangial cells (MC) are important mechanisms during nephrogenesis, for the maintenance of glomerular homeostasis as well as in renal disease and glomerular regeneration. Expression of chemokines and chemokine receptors by intrinsic renal cells, e.g. SLC/CCL21 on podocytes and CCR7 on MC is suggested to play a pivotal role during these processes. BMC Nephrology 2004, 5:8 http://www.biomedcentral.com/1471-2369/5/8 superfamily is separated into the C, CC, CXC, and CX3C subfamilies (Where X represents any intervening amino acid residue between the first two cysteines in the amino acid sequence) [5,6]. Chemokines mediate their biological activity by ligation and interaction with seven-transmembrane-spanning G protein-coupled receptors (i.e. C, CC, CXC, and CX3C receptors) [7]. Inducible expression of the chemokine receptor CCR1 by human MC was previously described [9]. Our group showed that SLC/CCL21 is constitutively expressed by glomerular podocytes and CCR7 constitutively expressed by MC [12]

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