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

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.

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

Background: Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown.

Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms.

Background: The blood brain barrier tightly regulates the passage of molecules into the brain and becomes leaky following obstructive cholestasis. The aim of this study was to determine if increased serum bile acids observed during cholestasis permeabilize the blood brain barrier.

Methods: Rats underwent bile duct ligation or deoxycholic or chenodeoxycholic acid injections and blood brain barrier permeability assessed.

The novel growth factor, progranulin, stimulates mouse cholangiocyte proliferation via sirtuin-1-mediated inactivation of FOXO1.

Progranulin (PGRN), a secreted growth factor, regulates the proliferation of various epithelial cells. Its mechanism of action is largely unknown. Sirtuin 1 (Sirt1) is a protein deacetylase that is known to regulate the transcriptional activity of the forkhead receptor FOXO1, thereby modulating the balance between proapoptotic and cell cycle-arresting genes.

Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism.

Background And Objectives: Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. The growth factor, progranulin, is overexpressed in a number of tumours. The study aims were to assess the expression of progranulin in cholangiocarcinoma and to determine its effects on tumour growth.

Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown.