Abstract
To investigate the effect and potential mechanism of human-derived urine stem cells (hUSCs) in inhibiting retinal aging by using experimental and bioinformatics. Retinal pigment epithelial cells cultured in vitro, which were randomly divided into normal group, aging group and supernatant of hUSCs group. Cell counting kit-8 detection, senescence-related β-galactosidase, and Annexin V/PI staining were performed to detect cell viability, senescence, and apoptosis. Subsequently, bioinformatics methods were used to explore the underlying mechanisms, in which, targets both hUSCs and aging retina-related targets were obtained from GeneCards. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein–protein interaction network were analysis, and the expressional level of hub gene was validated by q-PCR. Supernatant addition of hUSCs promoted markedly cellular proliferation, improved viability and inhibited senescence and apoptosis in vitro. A total of 1476 hUSCs-related targets (Relevance score > 20), 692 retinal disease-related targets, and 732 targets related to disease of aging were selected from GeneCards database, and 289 common targets of hUSCs against aging retina were confirmed through Venn analysis. Enrichment analysis demonstrated that hUSCs might exert its anti-apoptosis efficacy in multiple biological processes, including oxidative stress, inflammation and apoptosis, and core targets were associated with HIF-1, MAPK and PI3K-Akt signal. hUSCs inhibited retinal senescence by regulating multiply targets and signaling pathways, of these, HIF-1, MAPK, and PI3K may be important candidates.
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Abbreviations
- Akt:
-
AKT serine/threonine kinase 1
- BP:
-
Biological process
- CCK8:
-
Cell counting kit-8
- CC:
-
Cellular component
- CTNNB1:
-
Catenin beta 1
- cDNA:
-
Complementary deoxyribonucleic acid
- DPBS:
-
Dulbecco’s phosphate-buffered saline
- FN1:
-
Fibronectin 1
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- GO:
-
Gene Ontology
- HRAS:
-
HRAs proto-oncogene, guanosine triphosphate binding protein
- hUSCs:
-
Human-derived urine stem cells
- HIF-1:
-
Huntingtin interacting protein 1
- IL1B:
-
Interleukin 1 beta
- IL6:
-
Interleukin 6
- IL10:
-
Interleukin 10
- IBD:
-
Inflammatory bowel disease
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- MAPK:
-
Mitogen-activated protein kinase 1
- MF:
-
Molecular function
- RPE:
-
Retinal pigment epithelial
- PPI:
-
Protein–protein interaction
- PI3K:
-
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
- PBS:
-
Phosphate-buffered saline
- PTPN11:
-
Protein tyrosine phosphatase non-receptor type 11
- PIK3CA:
-
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
- qRT-PCR:
-
Quantitative real-time polymerase chain reaction
- ROS:
-
Reactive oxygen species
- SA-β-Gal:
-
Senescence-related β-galactosidase
- STAT3:
-
Signal transducer and activator of transcription 3
- TP53:
-
Tumor protein P53
- TNF:
-
Tumor necrosis factor
- VEGFA:
-
Vascular endothelial growth factor A
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Funding
This study was supported by a grant of talent item from Jinzhou medical university, also supported by a translational study of microRNA-target gene regulatory network in stroke and acute brain injury. Major Science and Technology Project of Sichuan Province (in the field of social development), Project No. 2020YFS0043, fund 1 million, period 2020.1–2022.12, principal: Ting-Hua Wang.
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LH and WTH conceived and designed the study. BN and LN conducted experiments; contributed the medicine. All authors read and approved the manuscript.
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All procedures were performed in accordance with the guidelines and approval of the Ethics Committee of the Kunming Medical University. Approved by the Animal Experiment Ethics Review Committee of Kunming Medical University, the approval number is KMMU20220854.
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Bi, N., Li, N., Liu, H. et al. Molecular Network Mechanism Analysis of Urine Stem Cells Against Retinal Aging. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10487-6
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DOI: https://doi.org/10.1007/s10528-023-10487-6