Gli1 activation and protection against hepatic encephalopathy is suppressed by circulating transforming growth factor β1 in mice.

ABSTRACT:

Background & aims

Hepatic encephalopathy (HE) is a neurologic disorder that develops during liver failure. Few studies exist investigating systemic-central signalling during HE outside of inflammatory signalling. The transcription factor Gli1, which can be modulated by hedgehog signalling or transforming growth factor β1 (TGFβ1) signalling, has been shown to be protective in various neuropathies. We measured Gli1 expression in brain tissues from mice and evaluated how circulating TGFβ1 and canonical hedgehog signalling regulate its activation.

Methods

Mice were injected with azoxymethane (AOM) to induce liver failure and HE in the presence of Gli1 vivo-morpholinos, the hedgehog inhibitor cyclopamine, Smoothened vivo-morpholinos, a Smoothened agonist, or TGFβ-neutralizing ant

SUBMITTER: McMillin M 

PROVIDER: S-EPMC4253574 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature