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HucMSC exosome-transported 14-3-3ζ prevents the injury of cisplatin to HK-2 cells by inducing autophagy in vitro
- Source :
- Cytotherapy. 20(1)
- Publication Year :
- 2017
-
Abstract
- Background aims On the basis of previous studies, exosomes secreted by human umbilical cord mesenchymal stromal cell (hucMSC-ex) could prevent and repair acute kidney injury induced by cisplatin in rats. However, its potential mechanism is still unclear. In the present study, the model with hucMSC-ex pretreated human renal tubular epithelial cell lines HK-2 that could prevent the injury of cisplatin was successfully established. Methods First, we pretreated the HK-2 cells with hucMSC-ex for 24 h. Cisplatin was then used to injure HK-2 cells. Gain and loss of function study were used to explore the role of 14-3-3ζ. The expression level of proliferating cell nuclear antigen (PCNA) was analyzed by immunofluorescence assay and Western blot. The number of apoptotic cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry analysis. The formation of autophagosomes was observed under super-resolution optical microscope. Western blot was used to analyze the expression levels of LC3B, P62, 14-3-3ζ and Bax. Results Pretreating cells with hucMSC-ex could prevent the injury of cisplatin by reducing the number of apoptotic cells and increasing the expression level of PCNA. Simultaneously, the autophagic level was up-regulated. The application of autophagic inhibitor 3-methyladenine (3-MA) could reverse the protective effect of hucMSC-ex. The overexpression of 14-3-3ζ enhanced the autophagic level and protected the injury of cisplatin. The knock-down of 14-3-3ζ could reduce the autophagic level and enhance the disadvantage of cisplatin. The enhanced injury of cisplatin was reversed when the knock-down of 14-3-3ζ was replenished with hucMSC-ex. Conclusions 14-3-3ζ transported by hucMSC-ex may up-regulate autophagic level in HK-2 cells, which can prevent the injury of cisplatin. This discovery provides the new theoretical basis for the prevention of cisplatin-induced nephrotoxicity by hucMSC-ex.
- Subjects :
- 0301 basic medicine
Cancer Research
Stromal cell
Immunology
Exosomes
Exosome
Umbilical Cord
03 medical and health sciences
Western blot
Autophagy
Immunology and Allergy
Medicine
Animals
Humans
Genetics (clinical)
Cisplatin
Transplantation
biology
medicine.diagnostic_test
business.industry
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Proliferating cell nuclear antigen
Rats
030104 developmental biology
HEK293 Cells
Oncology
Terminal deoxynucleotidyl transferase
14-3-3 Proteins
Apoptosis
Gene Knockdown Techniques
biology.protein
Cancer research
business
medicine.drug
Subjects
Details
- ISSN :
- 14772566
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cytotherapy
- Accession number :
- edsair.doi.dedup.....ad1712a8eb568c0c09644138200c0074