Pioglitazone increases VEGFR3 expression and promotes activation of M2 macrophages via the peroxisome proliferator‑activated receptor γ

Zhang,Conghui; Zhang,Ying; Zhang,Chunxiu; Liu,Yang; Liu,Yanyan; Xu,Gang

doi:10.3892/mmr.2019.9945

Pioglitazone increases VEGFR3 expression and promotes activation of M2 macrophages via the peroxisome proliferator‑activated receptor γ

Authors:
- Conghui Zhang
- Ying Zhang
- Chunxiu Zhang
- Yang Liu
- Yanyan Liu
- Gang Xu
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Affiliations: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Orthopedics, Tianjin Medical University General Hospital, Heping, Tianjin 300070, P.R. China
Published online on: February 7, 2019 https://doi.org/10.3892/mmr.2019.9945
Pages: 2740-2748
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The peroxisome proliferator‑activated receptor γ (PPARγ) agonist pioglitazone has been widely used in previous studies to ameliorate diabetes mellitus and regulate inflammation. However, the present study aimed to investigate the effect of pioglitazone on macrophages and determine its impact on renal fibrosis in vivo. Firstly, bone marrow‑derived macrophages (BMDM) were used to detect the effects of pioglitazone on macrophages in vitro. It was demonstrated that pioglitazone promoted M2 macrophage activation and induced vascular endothelial growth factor receptor 3 (VEGFR3) upregulation in a PPARγ‑dependent manner. Furthermore, pioglitazone increased macrophage proliferation and macrophage VEGFR3 expression in a murine unilateral ureteral obstruction (UUO) model; however, it had no therapeutic effect on renal fibrosis in vivo. Therefore, the results in the present study implied that presence of M2 macrophages may inhibit pioglitazone's ability to attenuate UUO‑induced renal fibrosis. In addition, the results demonstrated that macrophage‑associated VEGFR3 could be induced by pioglitazone, although it is still unclear what role VEGFR3+ M2 macrophages have in renal fibrosis.

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