Fig. 10.

Diagram of a signaling regulatory network that determines the AEC II differentiation phenotype. TGF-β1 promotes RILF via the induction of β-catenin to trigger AEC II transdifferentiation. After irradiation, TGF-β1 expression is induced. Subsequently, the suppression of E-cadherin and activation of β-catenin occur; as a result, Lin28 transcription is induced, which in turn, maintains AEC II stemness in order to promote injury repair by repressing let-7 via a mechanism that involves the mutual negative regulation of these molecules. On the other hand, significantly increased β-catenin expression is capable of inducing AEC II transdifferentiation by promoting the transcription of several profibrotic cytokine and factor genes. This is a fibrotic network. High levels of let-7 miRNAs are required for AEC II to AEC I differentiation. This pathway may occur during normal injury repair.