Additionally, there was evidence of perisinusoidal elastin deposition in both genotypes, albeit more prominent in the MMP-12 null mice. A similar distribution of perisinusoidal elastin was also seen following CCl4 administration in the knockout but not the WT animals. These
data show a striking similarity to our previous studies of the rr mutant mouse which secretes a collagen not susceptible to MMP degradation.30 In that model, prominent perisinusoidal collagen deposition was observed following induction of experimental fibrosis. Taken together, this suggests that the normal pattern of both elastin and collagen degradation as fibrosis remodels even in progressive disease is one in which perisinusoidal fibrosis is remodeled but there is relative resistance to degradation of the thicker and linear scars. The other striking finding from BTK inhibitor long-term administration of TAA to the MMP-12−/− animals was the increased accumulation of collagen in knockout compared with WT mice. This raises a number of interesting mechanistic questions. MMP-12 has been shown to have direct collagenolytic activity,31 and the observed differences may represent lack of this effect. However, one might have expected to see a similar difference
in collagen deposition following chronic CCl4 administration, which was not evident from our study. Furthermore, no compensatory increases in other find more MMPs in the MMP-12−/− mice were detected in our model, nor were changes in their global or activated protein levels as is described when other MMPs are deleted.32, 33 We have presented cogent evidence that elastin accumulates in advanced
liver injury but this occurs as a result of both synthesis and a failure of degradation. However, a level of degradation occurs and is mediated by MMP-12 derived from hepatic macrophages. Supporting this pathogenic model, MMP-12 knockout mice demonstrate significant elastin accumulation, highlighting mechanistically the importance of this enzyme in mediating elastin turnover during experimental fibrosis. These observations have important implications for the design of antifibrotic therapies. over Additional Supporting Information may be found in the online version of this article. “
“See article in J. Gastroenterol. Hepatol. 2012; 27: 1336–1340. Nodular regenerative hyperplasia (NRH) is characterized histologically by nodules of hyperplastic hepatocytes distributed throughout the liver with no fibrous septa in between the nodules.1 NRH can also be considered a component of intrahepatic portal venopathy, an entity which also includes diseases like non-cirrhotic portal fibrosis (NCPF) in the Indian subcontinent and idiopathic portal hypertension (IPH) in Japan.2 Overall, NRH is an uncommon condition with only a few hundred cases described in the world literature. Autopsy studies have shown NRH in 2.6% of autopsy livers with a higher prevalence (5.