Figure 4.
Low-dose decitabine upregulated the expression of downstream regulators of the LKB1 signaling pathway and inhibitory cytokines in MDSCs. (A-B) Representative western blots of MDSC LKB1 and GADPH in MDSCs from healthy controls and ITP patients, with or without decitabine modulation in vitro. Relative LKB1 protein expression, obtained via densitometry (Ctrl vs ITP, unpaired t test, ∗P = .0232; PBS vs decitabine, paired t test, ∗∗P = .0051). (C) LKB1 expression in CD11b+CD33+HLA-DRlow cells from healthy controls and ITP patients before and after decitabine treatment in vivo. LKB1 expression was significantly lower in ITP patients than in healthy controls (Ctrl vs ITP, unpaired t test, ∗P = .0474; before decitabine vs after decitabine, paired t test, ∗∗P = .0059). (D) The mRNA expression of proteins involved in the LKB1–AMPK signaling pathway in MDSCs cultured in vitro from ITP patients and healthy controls (Ctrl vs ITP: multiple unpaired t test, ∗PLKB1 = .0229, ∗∗PAMPKα1 = .0024, ∗∗∗PAMPKα2 = .0002, ∗∗∗∗PAMPKβ1 < .0001, ∗∗∗∗PAMPKβ2 < .0001, ∗∗∗∗PAMPKγ1 < .0001, ∗∗∗∗PAMPKγ2 < .0001, PAMPKγ3 = .0967, ∗∗∗∗PND-1 < .0001, ∗∗∗PND-3 = .0004, PND-6 = .0533, ∗∗PATP-6 = .0037), which (E) significantly increased after in vitro decitabine modulation in ITP patients (PBS vs decitabine: multiple paired t test,∗∗PLKB1 = .0048, ∗PAMPKα1 = .0341, PAMPKα2 = .1034, ∗PAMPKβ1 = .0489, ∗PAMPKβ2 = .0399, ∗∗PAMPKγ1 = .0019, ∗PAMPKγ2 = .0387, ∗∗PAMPKγ3 = .0047, ∗PND-1 = .0279, ∗PND-3 = .0276, ∗PND-6 = .0199, ∗PATP-6 = .0116). Likewise, (F) The level of inhibitory cytokines in MDSCs cultured in vitro from ITP patients and healthy controls (healthy control vs ITP: Multiple unpaired t test, ∗∗PIL-10 = .0027, ∗∗∗∗PTGF-β < .0001, ∗PVEGF = .0147), which (G) significantly increased after in vitro decitabine modulation in ITP patents (PBS vs decitabine: multiple unpaired t test, ∗PIL-10 = .0165, ∗PTGF-β = .0210, ∗PVEGF = .0298).

Low-dose decitabine upregulated the expression of downstream regulators of the LKB1 signaling pathway and inhibitory cytokines in MDSCs. (A-B) Representative western blots of MDSC LKB1 and GADPH in MDSCs from healthy controls and ITP patients, with or without decitabine modulation in vitro. Relative LKB1 protein expression, obtained via densitometry (Ctrl vs ITP, unpaired t test, ∗P = .0232; PBS vs decitabine, paired t test, ∗∗P = .0051). (C) LKB1 expression in CD11b+CD33+HLA-DRlow cells from healthy controls and ITP patients before and after decitabine treatment in vivo. LKB1 expression was significantly lower in ITP patients than in healthy controls (Ctrl vs ITP, unpaired t test, ∗P = .0474; before decitabine vs after decitabine, paired t test, ∗∗P = .0059). (D) The mRNA expression of proteins involved in the LKB1–AMPK signaling pathway in MDSCs cultured in vitro from ITP patients and healthy controls (Ctrl vs ITP: multiple unpaired t test, ∗PLKB1 = .0229, ∗∗PAMPKα1 = .0024, ∗∗∗PAMPKα2 = .0002, ∗∗∗∗PAMPKβ1 < .0001, ∗∗∗∗PAMPKβ2 < .0001, ∗∗∗∗PAMPKγ1 < .0001, ∗∗∗∗PAMPKγ2 < .0001, PAMPKγ3 = .0967, ∗∗∗∗PND-1 < .0001, ∗∗∗PND-3 = .0004, PND-6 = .0533, ∗∗PATP-6 = .0037), which (E) significantly increased after in vitro decitabine modulation in ITP patients (PBS vs decitabine: multiple paired t test,∗∗PLKB1 = .0048, ∗PAMPKα1 = .0341, PAMPKα2 = .1034, ∗PAMPKβ1 = .0489, ∗PAMPKβ2 = .0399, ∗∗PAMPKγ1 = .0019, ∗PAMPKγ2 = .0387, ∗∗PAMPKγ3 = .0047, ∗PND-1 = .0279, ∗PND-3 = .0276, ∗PND-6 = .0199, ∗PATP-6 = .0116). Likewise, (F) The level of inhibitory cytokines in MDSCs cultured in vitro from ITP patients and healthy controls (healthy control vs ITP: Multiple unpaired t test, ∗∗PIL-10 = .0027, ∗∗∗∗PTGF-β < .0001, ∗PVEGF = .0147), which (G) significantly increased after in vitro decitabine modulation in ITP patents (PBS vs decitabine: multiple unpaired t test, ∗PIL-10 = .0165, ∗PTGF-β = .0210, ∗PVEGF = .0298).

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