Mallory bodies (MBs) are characteristic of several liver disorders, and consist primarily of keratins with transglutaminase-generated keratin crosslinks. We tested the effect of the transglutaminase-2 (TG2) inhibitor KCC009 on MB formation in a mouse model fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). KCC009 decreased DDC-induced liver enlargement without affecting MB formation or extent of liver injury. TG2 protein and activity increased after DDC feeding and localized within and outside hepatocytes. KCC009 inhibited DDC-induced hepatomegaly by affecting hepatocyte cell size rather than proliferation. Hence, TG2 is a potential mediator of injury-induced hepatomegaly via modulation of hepatocyte hypertrophy, and KCC009-mediated TG2 inhibition does not affect mouse MB formation.
Bibliographical noteFunding Information:
We are grateful to Evelyn Resurrection for assistance with immunofluorescence staining. This work was supported by National Institutes of Health (NIH) Grant DK52951 and the Department of Veterans Affairs (M.B.O.), NIH Grant DK063198 (C.K.), Digestive Disease Center NIH Grant DK56339 and a European Molecular Biology Organization postdoctoral fellowship (P.S.).
- Mallory body
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
- Cell Biology