Fig. 6: CLU-induced OPCs and OL injury through inhibition of the PI3K-AKT pathway. | Nature Communications

Fig. 6: CLU-induced OPCs and OL injury through inhibition of the PI3K-AKT pathway.

From: Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases

Fig. 6

A–D Western blot confirmed a time-dependent reduction in p-PI3K, p-AKT, and p-mTOR after CLU stimulation (n = 3 technical replicates/group) (For p-mTOR/TOR, 1 h vs. 0 h p = 0.2193; 3 h vs. 0 h p = 0.0001; 6 h vs. 0 h p = 0.0335; 12 h vs. 0 h p = 0.0017; 24 h vs. 0 h p = 0.0001) (For p-ATK/AKT, 1 h vs. 0 h p = 0.3765; 3 h vs. 0 h p = 0.1101; 6 h vs. 0 h p = 0.0011; 12 h vs. 0 h p < 0.0001; 24 h vs. 0 h p < 0.0001) (For p-PI3K/PI3K, 1 h vs. 0 h p = 0.0155; 3 h vs. 0 h p = 0.0061; 6 h vs. 0 h p = 0.0008; 12 h vs. 0 h p = 0016; 24 h vs. 0 h p = 0007). E–I SC79 (an AKT agonist) could mitigate CLU damage to the OPC lineage, while MK2206 (an AKT antagonist) could exacerbate CLU damage to the OPC lineage in vivo (n = 4 mice/group) (For (F), DPBS vs. DPBS+MK2206 p = 0.0117, CLU vs. CLU+SC79 p = 0.0015, CLU+SC79 vs. CLU+MK2206 p = 0.0002) (For (G), DPBS vs. DPBS+MK2206 p = 0.0003, CLU vs. CLU+SC79 p < 0.0001, CLU vs. CLU+MK2206 p = 0.0005, CLU+SC79 vs. CLU+MK2206 p < 0.0001) (For (H), DPBS vs. CLU p < 0.0001, CLU vs. CLU+SC79 p = 0.0003, CLU+SC79 vs. CLU+MK2206 p < 0.0001) (For (I), DPBS vs. CLU p < 0.0001, CLU vs. CLU+SC79 p = 0.0006, CLU+SC79 vs. CLU+MK2206 p < 0.0001). For immunofluorescence pictures: Scale bar: 50 μm. Statistical analysis was performed using unpaired two-tailed Student’s t-tests, mean ± SD, *p < 0.05, **p < 0.01, ***p < 0.001. ns. = p not significant.

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