Rspo2 suppresses CD36-mediated apoptosis in oxidized low density lipoprotein-induced macrophages

Yan,Hui; Wang,Shuai; Li,Zhenwei; Sun,Zewei; Zan,Jie; Zhao,Wenting; Pan,Yanyun; Wang,Zhen; Wu,Mingjie; Zhu,Jianhua

doi:10.3892/mmr.2016.5642

Rspo2 suppresses CD36-mediated apoptosis in oxidized low density lipoprotein-induced macrophages

Authors:
- Hui Yan
- Shuai Wang
- Zhenwei Li
- Zewei Sun
- Jie Zan
- Wenting Zhao
- Yanyun Pan
- Zhen Wang
- Mingjie Wu
- Jianhua Zhu
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Affiliations: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Published online on: August 19, 2016 https://doi.org/10.3892/mmr.2016.5642
Pages: 2945-2952
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidized low density lipoprotein (oxLDL)-induced apoptosis of macrophages contributes to the formation of atherosclerotic plaques. R‑spondin 2 (Rspo2), a member of the cysteine‑rich secreted proteins, has been shown to be involved in the oncogenesis of several types of cancer. It has also been found to be abundantly expressed among the four R‑spondin members in macrophages. The present study was performed to determine whether Rspo2 is involved in the ox‑LDL‑induced apoptosis of macrophages. It was identified that Rspo2 inhibited oxLDL‑induced apoptosis in the presence of endoplasmic reticulum (ER) stress activator using flow cytometry. In addition, Rspo2 was observed to suppress oxLDL‑induced ER stress and reactive oxygen species production as demonstrated by western blotting. Furthermore, analysis of the role of Rspo2 in macrophage lipid uptake identified that Rspo2 negatively regulated the Dil‑oxLDL uptake by inhibiting the expression of cluster of differentiation (CD)36, through the transcription factor, peroxisome proliferator‑activated receptor (PPAR)‑γ. The manipulation of Rspo2 had a direct effect on PPAR‑γ nuclear translocation. In addition, chromatin immunoprecipitation analysis revealed that Rspo2 manipulation led to regulation of the direct binding between PPAR‑γ and CD36. In conclusion, Rspo2 was found to have a negative regulatory effect during oxLDL‑induced macrophage apoptosis by regulating lipid uptake.

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