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Cross-talk between TGFβ and IRE1α promotes HSC activation. 1, TGFβ-mediated phosphorylation of SMAD2/3 leads to increased expression of ECM proteins leading to ER stress. 2, ER stress leads to IRE1α autotransphosphorylation. 3, IRE1α signaling leads to phosphorylation of C/EBPβ downstream of ASK1 and JNK. 4, activation of C/EBPβ facilitates ECM production through a mechanism that involves p300. 5, together, this signaling cascade is critical for fibrogenesis.
