Strnad Pavel, Siegel Matthew, Toivola Diana M, Choi Kihang, Kosek Jon C, Khosla Chaitan, Omary M Bishr
Department of Medicine, Palo Alto VA Medical Center, Palo Alto, CA 94304, USA.
FEBS Lett. 2006 Apr 17;580(9):2351--2357. doi: 10.1016/j.febslet.2006.03.051.
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.
马洛里小体（MBs）是几种肝脏疾病的特征性表现，主要由具有转谷氨酰胺酶生成的角蛋白交联的角蛋白组成。我们在喂食3,5-二乙氧基羰基-1,4-二氢可力丁（DDC）的小鼠模型中测试了转谷氨酰胺酶-2（TG2）抑制剂KCC009对MB形成的影响。KCC009可减轻DDC诱导的肝脏肿大，但不影响MB的形成或肝损伤程度。DDC喂食后，TG2蛋白和活性增加，并定位于肝细胞内外。KCC009通过影响肝细胞大小而非增殖来抑制DDC诱导的肝肿大。因此，TG2是通过调节肝细胞肥大介导损伤诱导的肝肿大的潜在介质，而KCC009介导的TG2抑制不影响小鼠MB的形成。
