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. 2021 Feb 22;8:595634. doi: 10.3389/fmed.2021.595634

Figure 1.

Figure 1

Association of SIRT1-related signaling pathways and BPD. SIRT1 deacetylation activates PGC-1α, which continues to activate NRF1/2 and TFAM in turn, thus promoting mitochondrial biogenesis to improve BPD. SIRT1 activates AMPK, and after AMPK phosphorylation activates TSC1/2, TSC1/2 activates Nampt, and inhibits Rheb, thereby inhibiting the role of mTOR in suppressing autophagy. A certain amount of autophagy plays a protective role against BPD. After SIRT1 activates FOXOs, FOXOs may promote autophagy along with apoptosis, but Akt inhibits the pro-apoptotic effect of FOXOs. SIRT1 directly activates Akt through deacetylation. SIRT1 also inhibits the inhibitory effect of PTEN on PI3K by deacetylating PTEN, thereby enhancing PI3K phosphorylation of Akt. The activation of Akt ameliorates BPD by inhibiting apoptosis and inflammation. SIRT1 also inhibits the pro-apoptotic effect of p53. SIRT1 inhibits the pro-inflammatory effects of NF-κB and AP-1 by deacetylating p65, c-Fos, and c-Jun. The pro-apoptotic effect of AP-1 is also inhibited by SIRT1. SIRT1 inhibits TGF-β by deacetylating Smad, thereby suppressing fibrogenesis. In addition, the inhibition of TGF-β attenuates its role in promoting mTOR, which is also linked to fibrogenesis.