Fig. 7

HMGCS2 interacted with PPARα to facilitate lipid degradation metabolism in AECIIs. A, HMGCS2 was predicted to interacted with PPARα and the expression of HMGCS2 was positively associated with PPARα downstream genes CTP1A (R = 0.3668, P < 0.01) and CPT2 (R = 0.2757, P < 0.01) but not correlated to the expression of PPARα (R = 0.03, P = 0.49) in IPF cohort (GSE47460). B, The interaction between HMGCS2 and PPARα was further confirmed by IF co-localization and Co-ip, scale bar = 20 μm. C, CPT1A and CPT2 expression were recovered by adenoviral mediated expression of HMGCS2 in mice AECIIs in Bleomycin lung fibrosis model. D, L393V mutation abolished the interaction of HMGCS2 with PPARα and subsequently failed to recover CPT1A and CPT2 expression in A549 cells upon Bleomycin injury. E, L393V mutation HMGCS2 failed to inhibit the lipid accumulation in A549 cells upon Bleomycin treatment. Data are expressed as mean ± SD, *: p < 0.05; **: p < 0.01