Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation

P Strnad, M Siegel, Diana Toivola, K Choi, JC Kosek, C Khosla, MB Omary

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)

Abstract

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 NIB 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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)2351–2357
Number of pages7
JournalFEBS Letters
Volume580
Issue number9
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Keywords

  • transglutaminase
  • Mallory body
  • keratin

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