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. 2022 Oct 17;13:1028410. doi: 10.3389/fimmu.2022.1028410

Figure 5.

Figure 5

(A). Schematic illustration of the PI3K/Akt/mTOR signaling pathway. The activation of receptor tyrosine kinases (RTK) activates phosphatidylinositol 3-kinase (PI3K), which in turn phosphorylated PIP2 to PIP3 (89). While phosphatase and tensin homolog (PTEN) can dephosphorylate PIP3 (89). Then Akt is recruited to the plasma membrane and phosphorylated by mTORC2 (89, 90). Akt regulates several cellular processes through a variety of downstream proteins like glycogen synthase kinase 3-beta (GSK-3β), Forkhead Box O (FOXO) etc. (89) Besides, AKT can phosphorylate and inactivate RAS homolog enriched in brain (Rheb) and retention of the Rheb-GTP activates mTORC1 (89). Mechanical force shows association with Akt expression, but further investigation is needed to demonstrate the correlation (87). (Created with BioRender.com). (B) (a) Treatment with LY294002 (a PI3K inhibitor) markedly reduces the motility of human keratinocytes (91). (b) Expression of the differentiatuin marker involucrin increases in solvent-treated Myr-p110α*-mER cells (91). The 40OHT-treated Myr-p110α*-mER cells failed to induce involucrin protein expression under these conditions (91). (C) (a) Cell Counting Kit-8 analysis revealed that cell proliferation was inhibited by CUDC-907 at different concentrations, with significant differences among treatment groups (92). (b) Semi-quantitative analysis of the scratch assay results (n=20) (92). (c) CUDC-907 treatment decreased the production of COL1 and COL3 at 72 h post-treatment, as demonstrated by western blot analysis (92) (*p<0.05, **p<0.01 and ***p<0.001). (D) Hematoxylin and eosin, and immunohistochemical staining revealed fewer cell numbers, decreased deposition of COL1 and COL3, and fewer formed microvessels (n=15) (92). Magnification, ×200; scale bar=250 μm. Data are presented as the mean ± standard deviation of the mean. COL1, type I collagen; COL3, type III collagen; CD31, platelet endothelial cell adhesion molecule; CD34, hematopoietic progenitor cell antigen CD34 (92). NS, no significance.