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01-11-2020 | Obesity | Original Paper

Stromal cell-derived factor 1 (SDF1) attenuates platelet-derived growth factor-B (PDGF-B)-induced vascular remodeling for adipose tissue expansion in obesity

Authors: Eri Watanabe, Tsutomu Wada, Akira Okekawa, Fuka Kitamura, Go Komatsu, Yasuhiro Onogi, Seiji Yamamoto, Masakiyo Sasahara, Munehiro Kitada, Daisuke Koya, Hiroshi Tsuneki, Toshiyasu Sasaoka

Published in: Angiogenesis | Issue 4/2020

Abstract

Platelet-derived growth factor-B (PDGF-B) is a main factor to promote adipose tissue angiogenesis, which is responsible for the tissue expansion in obesity. In this process, PDGF-B induces the dissociation of pericytes from blood vessels; however, its regulatory mechanism remains unclear. In the present study, we found that stromal cell-derived factor 1 (SDF1) plays an essential role in this regulatory mechanism. SDF1 mRNA was increased in epididymal white adipose tissue (eWAT) of obese mice. Ex vivo pharmacological analyses using cultured adipose tissue demonstrated that physiological concentrations (1–100 pg/mL) of SDF1 inhibited the PDGF-B-induced pericyte dissociation from vessels via two cognate SDF1 receptors, CXCR4 and CXCR7. In contrast, higher concentrations (> 1 ng/mL) of SDF1 alone caused the dissociation of pericytes via CXCR4, and this effect disappeared in the cultured tissues from PDGF receptor β (PDGFRβ) knockout mice. To investigate the role of SDF1 in angiogenesis in vivo, the effects of anagliptin, an inhibitor of dipeptidyl peptidase 4 (DPP4) that degrades SDF1, were examined in mice fed a high-fat diet. Anagliptin increased the SDF1 levels in the serum and eWAT. These changes were associated with a reduction of pericyte dissociation and fat accumulation in eWAT. AMD3100, a CXCR4 antagonist, cancelled these anagliptin effects. In flow-cytometry analysis, anagliptin increased and decreased the PDGF-B expression in endothelial cells and macrophages, respectively, whereas anagliptin reduced the PDGFRβ expression in pericytes of eWAT. These results suggest that SDF1 negatively regulates the adipose tissue angiogenesis in obesity by altering the reactivity of pericytes to PDGF-B.

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Title: Stromal cell-derived factor 1 (SDF1) attenuates platelet-derived growth factor-B (PDGF-B)-induced vascular remodeling for adipose tissue expansion in obesity
Authors: Eri Watanabe
Tsutomu Wada
Akira Okekawa
Fuka Kitamura
Go Komatsu
Yasuhiro Onogi
Seiji Yamamoto
Masakiyo Sasahara
Munehiro Kitada
Daisuke Koya
Hiroshi Tsuneki
Toshiyasu Sasaoka
Publication date: 01-11-2020
Publisher: Springer Netherlands
Keywords: Obesity
Obesity
Published in: Angiogenesis / Issue 4/2020
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-020-09738-6

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