Title:Bioinformatics-based Study on the Effects of Umbilical Cord Mesenchymal Stem Cells on the Aging Retina
Volume: 19
Issue: 11
Author(s): Ya-Hui Shi, Jun-Qi Li, Min-Xu, Yu-Ying Wang, Ting-Hua Wang*, Zhong-Fu Zuo*Xue-Zheng Liu*
Affiliation:
- Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou,
121000, China
- Institute of Neuroscience, Kunming Medical University, Kunming, 650500, China
- Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou,
121000, China
- Institute of Neuroscience, Kunming Medical University, Kunming, 650500, China
- Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou,
121000, China
- Institute of Neuroscience, Kunming Medical University, Kunming, 650500, China
Keywords:
Retinal ganglion cells, aging, umbilical cord mesenchymal stem cells, bioinformatics analysis, apoptosis, oxidative stress.
Abstract:
Background: Retinal aging is one of the common public health problems caused by
population aging and has become an important cause of acquired vision loss in adults. The aim of
this study was to determine the role of human umbilical cord mesenchymal stem cells (hUCMSCs)
in delaying retinal ganglion cell (RGC) aging and part of the network of molecular mechanisms
involved.
Methods: A retinal ganglion cell senescence model was established in vitro and treated with
UCMSC. Successful establishment of the senescence system was demonstrated using β-
galactosidase staining. The ameliorative effect of MSC on senescence was demonstrated using
CCK8 cell viability and Annexin V-PI apoptosis staining. The relevant targets of RGC, MSC, and
senescence were mainly obtained by searching the GeneCards database. The protein interaction
network among the relevant targets was constructed using the String database and Cytoscape, and
10 key target genes were calculated based on the MCC algorithm, based on which Gene ontologies
(GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were
performed. Changes in relevant target genes were detected using real-time fluorescence quantitative
PCR and the mechanism of action of UCMSC was determined by RNA interference.
Results: β-galactosidase staining showed that UCMSC significantly reduced the positive results of
RGC. The retinal aging process was alleviated. The bioinformatics screen yielded 201 shared
genes. 10 key genes were selected by the MCC algorithm, including vascular endothelial growth
factor A (VEGFA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), albumin (ALB), interleukin-
6 (IL6), tumor necrosis factor (TNF), tumor protein P53 (TP53), insulin (INS), matrix metalloproteinase
9 (MMP9), epidermal growth factor (EGF), interleukin-1β (IL1B), and enrichment
to related transferase activity and kinase activity regulated biological processes involved in oxidative
stress and inflammation related pathways. In addition, PCR results showed that all the above
molecules were altered in expression after UCMSC involvement.
Conclusion: This experiment demonstrated the role of UCMSC in delaying retinal ganglion cell
senescence and further elucidated that UCMSC may be associated with the activation of VEGFA,
TP53, ALB, GAPDH, IL6, IL1B, MMP9 genes and the inhibition of INS, EGF, and TNF in delaying
retinal senescence.
