Liver and serum expression of matrix metalloproteinases in asymptomatic pediatric liver transplant recipients

Abstract

We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post-LT and age-matched controls for analyses of MMPs and TIMPs. Patients with fibrosis had significantly higher hepatic gene expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 than patients without. Expression of these genes correlated with graft Metavir fibrosis stage (r = 0.494-0.684, P ≤ 0.006 for all). Gene expression of MMP-1, MMP-3, MMP-8, TIMP-3, and TIMP-4 was undetectable in both patients and controls. Portal inflammation and cytokeratin 7 correlated positively with gene expression of TIMP-1. Gene expression of MMP-2, MMP-9, and TIMP-2 correlated negatively with the time of low-dose cortisone usage (r = -0.448 to -0.422, P < 0.05 for all). Serum concentrations of MMP-8 and TIMP-1 were significantly increased and MMP-9 decreased among patients compared with controls, but no correlations to graft histology or gene expression were observed. Hepatic gene expression of certain MMPs and TIMPs is increased in stable pediatric LT recipients displaying graft fibrosis, but this did not reflect to their serum concentrations. Increased hepatic gene expression of TIMP-1 correlated with graft fibrosis stage, inflammation, and chronic cholestasis.

Keywords: liver fibrosis; liver transplantation; matrix metalloproteinases; pediatric.