Molecular network regulation mechanism of Lycii Fructus in promoting directional differentiation of iris pigment epithelial cells to treat retinitis pigmentosa

doi:10.12092/j.issn.1009-2501.2019.12.013

Abstract

Abstract:

AIM: To investigate the molecular network regulation mechanism of Lycii Fructus (LF) in promoting directional differentiation of iris pigment epithelial cells in the treatment of retinitis pigmentosa(RP) based on the methods of bioinformatics and network pharmacology. METHODS: The main active ingredients and potential targets of LF were retrieved from TCMSP database and analysis platform. The data of GSE81058 gene expression profile was downloaded from GEO database. Volcanic maps and clustering thermal maps of differentially expressed genes between IPE and RPE were plotted by ggplot2 and Pheatmap packages, respectively. Protein-protein interaction (PPI) networks of LF component-target and IPE-RPE differentially expressed genes were constructed by STRING database. Cytoscape software was used to extract genes of the intersection network. Gene ontology and signaling pathway analysis of intersection genes were carried out through DAVID online database. CytoHubba was used to analyze the key targets of LF. RESULTS:A total of 188 chemical constituents of LF were obtained, of which 36 were the main active ingredients in blood. There were 201 possible targets for these active ingredients. 142 differentially expressed genes of IPE and RPE were obtained, of which 71 were up-regulated and 71 were down-regulated. 105 gene targets related to LF promoting IPE differentiation and treating RP were identified. The biological processes involved in LF acting on these targets included regulating cell differentiation and retinal layer formation. The related molecular functions mainly involved transcriptional co-activator activity, ion channel activity, etc. They were mainly concentrated in cytoplasm, Golgi apparatus, and other areas. The molecular mechanisms involved the regulation of PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction pathway, etc. The key targets of LF for IPE differentiation include SPP1, MMP9, SNAI2, etc.CONCLUSION: The gene expression profiles are of significant differences between IPE and RPE. The active ingredients of LF can act on these differentially expressed genes, promote IPE cells to differentiate into RPE, and thus treat RP. This study provides a scientific basis for the combination of cell transplantation and traditional Chinese medicine in the treatment of RP.

Key words: retinitis pigmentosa, bioinformatics, network pharmacology, iris pigment epithelial cells, retinal pigment epithelial cells, Lycii Fructus

CLC Number:

R965.2

SONG Houpan, ZENG Meiyan, CHEN Xiaojuan, CHEN Xinyi, PENG Jun, ZHOU Yasha, YANG Yijing, YANG Tao, CAI Xiong, PENG Qinghua. Molecular network regulation mechanism of Lycii Fructus in promoting directional differentiation of iris pigment epithelial cells to treat retinitis pigmentosa[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(12): 1402-1414.

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