A new study in which the area of liver and digestive diseases of the CIBER has participated (Ciberehd) has demonstrated the crucial role of the Stard1 protein in colestásic liver diseases (EHC), which usuallyn are accompanied by hepathocellular damage, fibrosis and cirrhosis due to the intracellular accumulation of solutes that cannot be excreted in bile, including bile acids (AB), which when accumulated in the liver They induce liver insufficiency by little known mechanisms.
In depth
There are therapeutic treatments available for EHC, but they are limitedsince the biochemical response to first -line treatment with ursodesoxicolic acid is associated with Important complications in approximately 40 percent of patients with primary bile collangitis (CBP), A rare form of EHC mediated by the immune system.
Now, researchers have discovered a key role in this protein. Specifically, it is a collaborative work between the group led by José C. Fernández-Checa (Iibb-CSIC-IDIBAPS-and José Juan García Marín (University of Salamanca), both of the area of liver and digestive diseases of the cyber (Ciberehd), with Laura Conde de la Rosa and Laura Fábrega as first authors.
Using samples of patients with CBP and Experimental models of complete obstructive cholestasis (Biliary ligation model, BDL) and chemically induced (DCC feeding), collaborative work demonstrates orn Stard1 crucial paper in hepatocellular lesion, inflammation and fibrosiswhich in turn entails the progression of the EHC.
More details
CBP patients show a greater expression of the liver levels of Stard1, and the genetic elimination of Stard1 in the hepatocytes of mice protects from the colosta hepatic lesion induced by the bile duration ligation (BDL) and the progression of the disease.
Bile acid synthesis (Bas) In the adult liver it is mainly done through what is known as the classical path. In this way, A key component is CYP7A1 proteinwhose activity increases after weaning, this being the step that regulates the production of Bas.
On the other hand, too There is an alternative route To produce these bile acids, which occurs in mitochondria. Unlike the classical route, this alternative is controlled by The amount of cholesterol available in the internal membrane of the mitochondria, whose regulation depends on the Stard1 protein.
When the Stard1 protein is activated in chronic liver disease (EHC), two key effects occur. First, biliary acid production is increased (Bas) by an alternative route. Secondly, glutathione is exhausted (GSH) In mitochondria due to the accumulation of cholesterol, which makes cell membranes lose flexibility. This change in the membrane makes liver cells more vulnerable to toxicity and inflammation caused by bile acids.
To take into account
“The findings’In vivo‘With bile duct block (BDL) they reproduced’ in vitro ‘in primary mouse hepatocytes cultivated with pharmacological exhaustion of mitochondrial GSH, which unmasked its sensitivity to cytotoxicity and inflammation induced by BA, BA, as well as DNA damage revealed by the length of the comet’s tail“The researchers explained.
Thus, the team ensures that its findings “They identify a previously unrecognized role for Stard1 in cholestasis and suggest that addressing Stard1 can be a novel approach to EHC“
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