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Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis

Gonzalez, J., Mouttalib, S., Delage, C., Calise, D., Maoret, J-J., Pradere, J-P., Klein, J., Buffin-Meyer, B., Van der Veen, B., Charo, I. F., Heeringa, P., Duchene, J., Bascands, J-L. & Schanstra, J-P., 23-Aug-2013, In : Biochemical and Biophysical Research Communications. 438, 2, p. 257-263 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Julien Gonzalez
  • Sofia Mouttalib
  • Christine Delage
  • Denis Calise
  • Jean-Jose Maoret
  • Jean-Philippe Pradere
  • Julie Klein
  • Benedicte Buffin-Meyer
  • Betty Van der Veen
  • Israel F. Charo
  • Peter Heeringa
  • Johan Duchene
  • Jean-Loup Bascands
  • Joost-Peter Schanstra

Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can also have a beneficial anti-fibrotic role depending in particular on the stage of the pathology. Chemokines play an important role in monocyte extravasation in the inflammatory process. CCL2 has already been shown to be involved in the development of TIF but CCL7, a close relative of CCL2 and able to bind to similar receptors, has not been studied in renal disease. We therefore studied chemokine CCL7 in a model of unilateral ureteral obstruction (UUO)-induced TIF. We observed that the role of CCL7 differs depending on the stage of the pathology. In early stages (0-8 days), CCL7 deficient (CCL7-KO) mice displayed attenuated TIF potentially involving two mechanisms: an early (0-3 days) decrease of inflammatory cell infiltration followed (3-8 days) by a decrease in tubular ECM production independent of inflammation. In contrast, during later stages of obstruction (10-14 days), CCL7-KO mice displayed increased TIF which was again associated with reduced inflammation. Interestingly, the switch between this anti- to profibrotic effect was accompanied by an increased influx of immunosuppressive regulatory T cells. In conclusion, these results highlight for the first time a dual role for CCL7 in the development of renal TIF, deleterious in early stages but beneficial during later stages. (C) 2013 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume438
Issue number2
Publication statusPublished - 23-Aug-2013

    Keywords

  • Inflammation, Fibrosis, Kidney, MONOCYTE CHEMOATTRACTANT PROTEIN-1, REGULATORY T-CELLS, PLASMINOGEN-ACTIVATOR INHIBITOR-1, OBSTRUCTIVE NEPHROPATHY, CHEMOTACTIC PROTEIN-3, INTERSTITIAL FIBROSIS, FIBROBLAST COLLAGEN, PULMONARY-FIBROSIS, BONE-MARROW, EXPRESSION

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