Fig. 7: lnc668-PICALM-mediated pulmonary fibrogenesis depended on YTHDC1 phase separation.

a Immunofluorescence detection uncovered that si-lnc668 reduced the expression of PICALM in cells. b PICALM expression was inhibited by si-lnc668 and promoted by overexpression in vivo and in vitro. c qRT-PCR showed that si-lnc668 reduced PICALM mRNA expression. d Half-life analysis revealed that PICALM mRNA stability was enhanced by TGF-β1 but reduced by si-lnc668. e Rescue experiments confirmed that si-lnc668 reduced the expression levels of PICALM, FAP, VIM, α-SMA, COL1A, and COL3A. PICALM overexpression increased the expression levels of these proteins. f Western blot analysis confirmed that si-YTHDC1 significantly reduced the elevated levels of YTHDC1, PICALM, FAP, VIM, α-SMA, COL1A, and COL3A induced by TGF-β1 stimulation. The overexpression of YTHDC1 increased the expression levels of PICALM, FAP, VIM, α-SMA, COL1A, and COL3A. However, YTHDC1-Δ274-294 overexpression did not increase the expression levels of YTHDC1, PICALM, FAP, VIM, α-SMA, COL1A, and COL3A. g Western blot rescue experiments indicated that si-YTHDC1 led to the decreased expression levels of FAP, VIM, α-SMA, PICALM, COL1A, and COL3A. Conversely, overexpressed YTHDC1 elevated the expression levels of these proteins, counteracting the suppressive effect of si-YTHDC1. However, the YTHDC1-∆274-294 overexpression mutant failed to increase the expression levels of these proteins and did not counteract the suppressive effect of si-YTHDC1. h Rescue experiments confirmed that METTL3 overexpression increased the expression levels of FAP, VIM, α-SMA, COL1A, and COL3A. si-YTHDC1 reduced the expression of lnc668, reversing the effect of METTL3 on the above proteins.