Fig. 7

P311 was upregulated by several common injury signals. a Primary mouse EpSCs were stimulated using 10 ng/ml IL-1β, IL-6, or TNFα or cultured in 2% O₂ for 72 hours. Total RNA was extracted from the cells and analyzed using real-time PCR (n = 4 per group). Data shown as mean ± SEM, Student’s t test; *P < 0.05 and **P < 0.01 vs control group. b Model illustrating that P311 is involved in regulating the transdifferentiation of EpSCs into MFLCs via a TGFβ1-dependent process. In a normal state, TGFβ1 transcription is steady but TGFβ1 mRNA is poorly translated because it has long 5′/3′ UTRs. When EpSCs are stimulated with cytokines or hypoxia, P311 is upregulated. Although P311 slightly decreases TGFβ1 transcription by enhancing the methylation of the TGFβ1 promoter, P311 significantly increases the expression of the TGFβ1 protein by activating its 5′/3′ UTRs. Expression of TβRI/II and activity of Smad2/3 are subsequently enhanced indirectly by higher levels of active TGFβ1 or directly by P311. Smad2/3 is then translocated into the nucleus, where it upregulates myofibroblast markers (e.g., vimentin and α-SMA) and downregulates EpSC markers (e.g., E-cadherin and β1integrin) to promote the transdifferentiation of EpSCs into MFLCs. UTR untranslated region