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Pivotal role of the CCL5/CCR5 interaction for recruitment of endothelial progenitor cells in mouse wound healing
Yuko Ishida, … , Naofumi Mukaida, Toshikazu Kondo
Yuko Ishida, … , Naofumi Mukaida, Toshikazu Kondo
Published January 3, 2012
Citation Information: J Clin Invest. 2012;122(2):711-721. https://doi.org/10.1172/JCI43027.
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Research Article Dermatology

Pivotal role of the CCL5/CCR5 interaction for recruitment of endothelial progenitor cells in mouse wound healing

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Abstract

BM-derived endothelial progenitor cells (EPCs) are critical and essential for neovascularization in tissue repair and tumorigenesis. EPCs migrate from BM to tissues via the bloodstream, but specific chemotactic cues have not been identified. Here we show in mice that the absence of CCR5 reduced vascular EPC accumulation and neovascularization, but not macrophage recruitment, and eventually delayed healing in wounded skin. When transferred into Ccr5–/– mice, Ccr5+/+ BM cells, but not Ccr5–/– cells, accumulated in the wound site, were incorporated into the vasculature, and restored normal neovascularization. Consistent with these observations, CCL5 induced in vitro EPC migration in a CCR5-dependent manner. Moreover, expression of VEGF and TGF-β was substantially diminished at wound sites in Ccr5–/– mice, which suggests that EPCs are important not only as the progenitors of endothelial cells, but also as the source of growth factors during tissue repair. Taken together, these data identify the CCL5/CCR5 interaction as what we believe to be a novel molecular target for modulation of neovascularization and eventual tissue repair.

Authors

Yuko Ishida, Akihiko Kimura, Yumi Kuninaka, Masanori Inui, Kouji Matsushima, Naofumi Mukaida, Toshikazu Kondo

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Figure 1

CCR5 expression at wound sites in WT mice.

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CCR5 expression at wound sites in WT mice.
(A) Quantitative RT-PCR analy...
(A) Quantitative RT-PCR analysis for Ccr5 mRNA (n = 6). (B) Western blotting analysis of CCR5 protein expression. Representative results from 6 independent experiments are shown. (C) CCR5/α-tubulin ratios, calculated densitometrically (n = 6 independent experiments). (D) Cell types expressing CCR5 in wounded skin at day 6. Triple-color immunofluorescence images of CCR5 (green), CD31 (red), and F4/80 (blue). Representative results from 4 individual animals are shown. Original magnification, ×400. All values represent mean ± SEM. **P < 0.01 versus uninjured skin (time 0).

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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