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Molecular Network Mechanism Analysis of Urine Stem Cells Against Retinal Aging

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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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Authors and Affiliations

  1. Institute of Neuroscience, Kunming Medical University, Kunming, 650500, China

    Ning Bi & Ting-Hua Wang

  2. Animal Center, Kunming Medical University, Kunming, 650500, China

    Na Li & Ting-Hua Wang

  3. Department of Anatomy, College of Basic Medicine, Jinzhou Medical University, Jinzhou, 121000, China

    Na Li, Hua Liu & Ting-Hua Wang

Authors
  1. Ning Bi
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  2. Na Li
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  3. Hua Liu
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  4. Ting-Hua Wang
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Contributions

LH and WTH conceived and designed the study. BN and LN conducted experiments; contributed the medicine. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Hua Liu or Ting-Hua Wang.

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Conflict of Interest

There is no conflict interest in this study.

Ethical Approval and Consent for Participation

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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