Islet-cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice.

Regeneration is a unique defense mechanism of liver tissue in response to functional cell loss induced by toxic chemicals or surgical resection. In this study, we found that Islet-cell autoantigen 69 (Ica69) accelerates liver regeneration in mice. Following 70% partial hepatectomy, both Ica69 mRNA and protein are significantly upregulated in mouse hepatocytes at the early stage of liver regeneration. Compared with the wild-type mice, Ica69-deficient mice have more severe liver injury, delayed liver regeneration, and high surgical accidental mortality following hepatectomy. Mechanistically, Ica69 interacts with Pick1 protein to regulate Tgfbr1 protein expression and Tgf beta-induced Smad2 phosphorylation. Our findings suggest that Ica69 in liver tissue is a new potential target for promoting liver regeneration.