PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R

Zhang,Yiqian; Li,Yufeng; Liu,Zhiwei; Zhao,Qixiang; Zhang,Hao; Wang,Xiaoyu; Lu,Peng; Yu,Hongli; Wang,Meng; Dong,Hongyan; Zhang,Zhongming

doi:10.3892/mmr.2018.8733

PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by inducing autophagy related 5-mediated autophagy via PEDF-R

Authors:
- Yiqian Zhang
- Yufeng Li
- Zhiwei Liu
- Qixiang Zhao
- Hao Zhang
- Xiaoyu Wang
- Peng Lu
- Hongli Yu
- Meng Wang
- Hongyan Dong
- Zhongming Zhang
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Affiliations: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Thoracic Cardiovascular Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China, Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
Published online on: March 14, 2018 https://doi.org/10.3892/mmr.2018.8733
Pages: 7170-7176
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pigment epithelial-derived factor (PEDF) is a multifunctional secreted glycoprotein, which exerts a variety of physiological activities. PEDF may protect against hypoxia‑induced cell death associated with its antioxidative effects and p53 mitochondrial translocation in cultured cardiomyocytes and H9c2 cells. Additionally, previous studies have suggested that autophagy is an important cell survival mechanism. However, the effect of PEDF on autophagy and the associated pathway in hypoxic H9c2 cells has not been fully established. Autophagy has been reported to regulate lipid metabolism; however, little is known about whether PEDF is able to regulate lipid metabolism by promoting autophagy. In the present study, western blotting results revealed that PEDF increased the level of microtubule‑associated protein 1A/1B‑light chain 3 (LC3)‑II. Transmission electron microscopy (TEM) and LC3 fluorescence demonstrated that PEDF increased the number of autophagosomes. PEDF also increased the viability of hypoxic H9c2 cells and decreased the level of cleaved caspase‑3 protein, as evidenced by CCK‑8 assays and western blotting, respectively. TEM and a triglyceride assay kit demonstrated that PEDF‑induced autophagy may stimulate lipid degradation. Western blotting results revealed a novel mechanism underlying PEDF‑induced H9c2 cell autophagy via the PEDF‑R‑mediated Atg5 pathway under hypoxic conditions. Furthermore, the results also suggest that PEDF‑induced autophagy may stimulate lipid degradation. The survival function of autophagy suggests that modulation of PEDF‑induced autophagy may be used as a therapeutic strategy to protect cells against lipid-associated metabolic diseases.

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