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. 2023 Feb 13;12(4):806.
doi: 10.3390/foods12040806.

Role of PI3K-AKT Pathway in Ultraviolet Ray and Hydrogen Peroxide-Induced Oxidative Damage and Its Repair by Grain Ferments

Wenjing Cheng  1   2 , Xiuqin Shi  1   2 , Jiachan Zhang  1   2 , Luyao Li  1   2 , Feiqian Di  1   2 , Meng Li  1   2 , Changtao Wang  1   2 , Quan An  3 , Dan Zhao  1   2
Affiliations

Role of PI3K-AKT Pathway in Ultraviolet Ray and Hydrogen Peroxide-Induced Oxidative Damage and Its Repair by Grain Ferments

Wenjing Cheng et al. Foods. .

Abstract

UV and external environmental stimuli can cause oxidative damage to skin cells. However, the molecular mechanisms involved in cell damage have not been systematically and clearly elucidated. In our study, an RNA-seq technique was used to determine the differentially expressed genes (DEGs) of the UVA/H2O2-induced model. Gene Oncology (GO) clustering and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were performed to determine the core DEGs and key signaling pathway. The PI3K-AKT signaling pathway was selected as playing a part in the oxidative process and was verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We selected three kinds of Schizophyllum commune fermented actives to evaluate whether the PI3K-AKT signaling pathway also plays a role in the resistance of active substances to oxidative damage. Results indicated that DEGs were mainly enriched in five categories: external stimulus response, oxidative stress, immunity, inflammation, and skin barrier regulation. S. commune-grain ferments can effectively reduce cellular oxidative damage through the PI3K-AKT pathway at both the cellular and molecular levels. Some typical mRNAs (COL1A1, COL1A2, COL4A5, FN1, IGF2, NR4A1, and PIK3R1) were detected, and the results obtained were consistent with those of RNA-seq. These results may give us a common set of standards or criteria for the screen of anti-oxidative actives in the future.

Keywords: PI3K-Akt pathway; RNA-seq; antioxidant; grain fermentation.

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Conflict of interest statement

The author Quan An was employed by the company Yunnao Baiyao Group Co, Ltd. He took part in the visualization of the data in the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The toxicity of UVA (A), H2O2 (B) to HSF cells, and the diagrams of the DEG GO terms (C–F). The results were expressed as mean ± SD (n = 6). The Model in (A) was established by UVA (15 J/cm2) irradiation; and the Model in (B) was established by H2O2 (1000 μmol/L for 30 min) treatment. In the bubble diagram, the vertical axis indicated GO terms and the horizontal axis represented gene ratio involved in each term. The size of dots indicated the number of genes in the GO term. The color of dots exhibited the significance. (C,E), differentially upregulated genes; (D,F), differently downregulated genes.
Figure 2
Figure 2
Bar diagrams and bubble diagrams of KEGG pathway enrichment analysis of UVA-induced (A–C) and H2O2-induced (D–F) DEGs. (A, D), differentially upregulated genes in each study; (B,E), differently downregulated genes in each study. In the bubble diagram, the vertical axis indicated GO terms and the horizontal axis represented gene ratio involved in each term. The size of dots indicated the number of genes in the GO term. The color of dots exhibited the significance. (C,F), the top 10 ranked KEGG terms of both upregulated and downregulated DEGs. In the bar diagram, the right vertical axis indicated the significance of each term by exhibiting a value of −log10(P), and the left vertical axis showed the number of genes involved in each term. The horizontal axis represented the top 10 ranked KEGG terms.
Figure 3
Figure 3
PI3K-AKT Signaling Pathway in UVA-induced(A) and H2O2-induced(B) model. Red: upregulated gene; Yellow: downregulated gene; Green: not regulated significantly gene.
Figure 4
Figure 4
The toxicity of RFB (A), HBFB (B) and OFB (C) to HSF cells and the repair effects of RFB (D), HBFB (E), and OFB (F) on UVA-induced and H2O2-induced oxidative stress damage in HSF cells. The results were expressed as mean ± SD (n = 6). The discussed concentrations of RFB, HBFB and OFB were 0.625 mg/mL, 0.625 mg/mL, and 0.32 mg/mL, respectively. **, p < 0.01, UVA/H2O2-induced model compared with the DMEM-treated control. # p < 0.05, and ## p < 0.01, RFB, HBFB, OFB compared with the Model.
Figure 5
Figure 5
The relative gene expression changes after the repair of rice fermentation broth (RFB, A), highland barley fermentation broth (HBFB, B) and oats fermented broth (OFB, C) on UVA and H2O2 injury. RFB, HBFB, and OFB are three kinds of S. commune fermentation broths. Genes, COL1A1 (A-1, B-1, C-1), COL1A2 (A-2, B-2, C-2), PIK3R1 (A-3, B-3, C-3), FN1 (A-4, B-4, C-4), IGF2 (A-5, B-5, C-5) and COL4A5 (A-6, B-6, C-6) were measured. The UVA bar represented the model established by UVA (15 J/cm2) treatment; the H2O2 bar represented the model established by H2O2 (1000 µmol/L for 30 min) treatment. **, p < 0.01, the UVA/H2O2-induced model compared with the DMEM-treated control. ## p < 0.01 and n.s. p > 0.05, RFB, HBFB, and OFB treated cells compared with the Model.
Figure 6
Figure 6
RFB, HBFB and OFB influence the signaling pathways of UVA/H2O2-induced skin oxidative damage. RFB, HBFB, and OFB are three kinds of S. commune fermentation broths. RFB, rice fermentation broth; HBFB, highland barley fermentation broth; OFB, oats fermented broth.
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