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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