Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation.
Pavel Strnad, Matthew Siegel, Diana M Toivola, Kihang Choi, Jon C Kosek, Chaitan Khosla, M Bishr Omary
Department of Medicine, Palo Alto VA Medical Center, Palo Alto, CA 94304, USA.
FEBS letters 2006 Apr 17Mallory 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.
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Pavel Strnad, Matthew Siegel, Diana M Toivola, Kihang Choi, Jon C Kosek, Chaitan Khosla, M Bishr Omary. Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation. FEBS letters. 2006 Apr 17;580(9):2351--2357
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PMID: 16616523
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