Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases.

ABSTRACT:

Objective

Polycystic liver diseases (PCLDs) are genetic disorders characterised by progressive bile duct dilatation and/or cyst development. Their pathogenesis is a consequence of hyperproliferation, hypersecretion and microRNA alterations in cholangiocytes. Here we evaluate the role of matrix metalloproteases (MMPs) in the hepatic cystogenesis of PCLDs.

Design

Metalloprotease activity was measured by microfluorimetric assays in normal and polycystic cholangiocyte cultures from humans and rats, and gene expression by real time quantitative PCR. The role of cytokines, oestrogens and growth factors present in the cystic fluid of PCLD patients was evaluated for MMP activity. The MMP inhibitor marimastat was examined for cystic expansion in vitro and in polycystic kidney (PCK) r

SUBMITTER: Urribarri AD 

PROVIDER: S-EPMC4362729 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature