Extended Data Fig. 8: The STING-PERK-eIF2α cascade underlies pulmonary and renal fibrosis.

(A-D) Immunofluorescence imaging showed the cGAMP-triggered upregulation of endogenous α-SMA and collagen I proteins in lung sections, which were substantially dampened in PERK half-deficiency mice (A-B), or upon the treatment of the PERK inhibitor iPERK-2 (C-D). Scale bars=100 μm. Data in A-D represent three independent experiments. (E) As expected, the kidney collected from the UUO surgery group on day 14 was dilated. Scale bars=1 cm. Data shown represent n = 13 mice in the sham group; n = 16 mice in other groups. (F) A schematic figure describing the signalling mechanism and function of this non-canonical cGAS-STING-PERK pathway, which occurred at the ER to regulate mRNA translation and preceded to the classical STING-TBK1-IRF3 cascade that regulates mRNA transcription.