p53 mediates PEDF-induced autophagy in human umbilical vein endothelial cells through sestrin2 signaling
| Autor: | Tianbo Li, Jiangning Wang, Tiangui Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
p53 Cancer Research pigment epithelium-derived factor autophagy Cell Cycle Proteins Biochemistry 03 medical and health sciences 0302 clinical medicine PEDF Western blot Sequestosome-1 Protein Genetics medicine Human Umbilical Vein Endothelial Cells Humans Nerve Growth Factors Phosphorylation RNA Small Interfering Eye Proteins Molecular Biology Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Serpins Adaptor Proteins Signal Transducing Regulation of gene expression medicine.diagnostic_test biology Chemistry TOR Serine-Threonine Kinases EIF4E Autophagy Nuclear Proteins Ribosomal Protein S6 Kinases 70-kDa Transfection Articles Cell biology 030104 developmental biology Oncology Gene Expression Regulation sestrin2 030220 oncology & carcinogenesis biology.protein Molecular Medicine Tumor Suppressor Protein p53 Microtubule-Associated Proteins Signal Transduction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Autophagy is a conserved catabolic process by which cytoplasmic components are delivered into lysosomes for degradation. Pigment epithelium‑derived factor (PEDF) has been reported to be associated with autophagy and can induce p53 expression; however, the mechanism relating PEDF with autophagy in endothelial cells remains poorly understood. The present study aimed to investigate the association between the PEDF‑p53‑sestrin pathway and autophagy in human umbilical vein endothelial cells (HUVECs). PEDF‑induced autophagy was examined by fluorescence microscopy and western blot analysis. p53 small interfering (si)RNA and sestrin2 siRNA were constructed and transfected into HUVECs prior to PEDF treatment. The protein expression levels of microtubule‑associated protein light chain 3 (LC3) I, LC3 II and p62 were evaluated by western blot analysis, and the mRNA expression levels of p53 and sestrin2 were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The regulation of mechanistic target of rapamycin (mTOR) was reflected by p70S6 kinase (p70S6K) and eukaryotic translation initiation factor 4E‑binding protein 1 (4E‑BP1) protein expression levels, as determined by western blot analysis. PEDF could induce HUVEC autophagy by sequentially inducing p53 and sestrin2 expression, as observed by fluorescence microscopy and western blot analysis. Conversely, the induction of sestrin2 by PEDF was eliminated by p53 siRNA. In addition, p53 siRNA and sestrin2 siRNA could attenuate PEDF‑induced HUVEC autophagy. Inhibition of mTOR may be the mechanism responsible for PEDF‑induced autophagy; as p70S6K and 4E‑BP1 phosphorylation levels were significantly upregulated in p53 siRNA‑treated and sestrin2 siRNA‑treated groups. The findings of the present study indicated that PEDF may trigger autophagy in HUVECs by inducing p53 and sestrin2 expression, and inhibiting mTOR expression; these findings may contribute to the improved understanding of diseases, including cancer and atherosclerosis. |
| Databáze: | OpenAIRE |
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