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

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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.