ALKBH5 Exacerbates Aortic Dissection by Promoting Inflammatory Response and Apoptosis of Aortic Smooth Muscle Cells via Regulating lnc-TMPO-AS1/EZH2/IRAK4 Signals in an m6A Modification Manner

Figure 6

IRAK4 is positively correlated with ALKBH5 in terms of expression level and biological function. (a, b) The expression level of IRAK4 in 40 pairs of aorta tissues from AD patients and donors was measured and confirmed its negative correlation with ALKBH5 expression by Pearson’s correlation coefficient analysis (, ). (c) Overexpressing ALKBH5 promoted the expression of IRAK4 while ALKBH5 knockdown suppressed it. (d) The effects of interference on mRNA and protein levels of IRAK4 were confirmed. (e, f) IRAK4 could further promote AngII-induced HASMC apoptosis increased by ALKBH5 overexpression, while IRAK4 knockdown partly counteracted the proapoptotic effect caused by the overexpression of AKLBH5. (g, h) Overexpression of IRAK4 enhanced the hypersecretion of inflammatory cytokines and the high expression of inflammation-related genes caused by ALKBH5 overexpression while silencing IRAK4 could partially offset the proinflammatory effect of ALKBH5. (i) The level of pNFκB was upregulated by ALKBH5, and this effect could be further enhanced by the overexpression of IRAK4 or weakened by its knockdown. (j, k) IRAK4 overexpression or knockdown enhanced or partly offset the influences of ALKBH5 upregulation on the incidence of AD and survival time in mice. Data represented the from three independent experiments, .

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