{"id":6761,"date":"2025-01-15T13:16:14","date_gmt":"2025-01-15T13:16:14","guid":{"rendered":"https:\/\/ibsal.es\/key-role-of-stard1-protein-discovered-in-cholestatic-liver-diseases\/"},"modified":"2025-03-10T17:29:40","modified_gmt":"2025-03-10T17:29:40","slug":"key-role-of-stard1-protein-discovered-in-cholestatic-liver-diseases","status":"publish","type":"post","link":"https:\/\/ibsal.es\/en\/key-role-of-stard1-protein-discovered-in-cholestatic-liver-diseases\/","title":{"rendered":"Key role of Stard1 protein discovered in cholestatic liver diseases"},"content":{"rendered":"\n<p><strong>The work is led by Jos\u00e9 Juan Garc\u00eda Mar\u00edn (USAL-IBSAL) and Jos\u00e9 C. Fern\u00e1ndez-Checa (IIBB-CSIC-IDIBAPS-), both from the Hepatic and Digestive Diseases area of the CIBER (CIBEREHD).<\/strong><\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p><strong>Hepatology&#8217; reports the research whose first authors are the scientists Laura Conde de la Rosa and Laura F\u00e1brega.<\/strong><\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>Cholestatic liver diseases (CLD) are often accompanied by hepatocellular damage, fibrosis and cirrhosis due to intracellular accumulation of solutes that cannot be excreted in bile, including bile acids (BA), which when accumulated in the liver induce liver failure by poorly understood mechanisms.<\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>Therapeutic treatments are available for EHC, but are limited, as biochemical response to first-line treatment with ursodeoxycholic acid is associated with major complications in approximately 40% of patients with primary biliary cholangitis (PBC), a rare form of immune-mediated EHC.<\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>Now, a new study recently published in the renowned scientific journal <em>Hepatology<\/em> shows a crucial role of the Stard1 protein in cholestatic liver diseases. This is a collaborative work developed between the group led by Jos\u00e9 C. Fern\u00e1ndez-Checa (IIBB-CSIC-IDIBAPS-) and Jos\u00e9 Juan Garc\u00eda Mar\u00edn, director of the HEVEPHARM research group (USAL-IBSAL), both from the Hepatic and Digestive Diseases area of CIBER (Centro Nacional de Investigaci\u00f3n Biom\u00e9dica en Red para el Estudio de Enfermedades Hep\u00e1ticas y Digestivas, CIBEREHD), with the scientists Laura Conde de la Rosa and Laura F\u00e1brega as first authors.   <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>Using samples from PBC patients and experimental models of complete obstructive (bile duct ligation model, BDL) and chemically induced (DCC feeding) obstructive cholestasis, the study demonstrates a crucial role of Stard1 in hepatocellular injury, inflammation and fibrosis, which in turn leads to the progression of HCD. PBC patients show increased expression of hepatic levels of Stard1, and genetic deletion of Stard1 in mouse hepatocytes protects against bile duct ligation (BDL)-induced cholestatic liver injury and disease progression.   <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>The synthesis of bile acids (BAs) in the adult liver is mainly carried out through what is known as the classical pathway. In this pathway, a key component is the CYP7A1 protein, whose activity increases after weaning, this being the step that regulates the production of BAs. <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>On the other hand, there is also an alternative pathway for producing these bile acids, which occurs in the mitochondria. Unlike the classical pathway, this alternative is controlled by the amount of cholesterol available in the inner membrane of the mitochondria, whose regulation depends on the Stard1 protein.   <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p><strong>Key effects<\/strong><\/p>\n\n<p>When the Stard1 protein is activated in chronic liver disease (CLD), two key effects occur. First, the production of bile acids (BAs) is increased via an alternative pathway. Second, glutathione (GSH) is depleted in mitochondria due to cholesterol accumulation, causing cell membranes to lose flexibility. This membrane change makes liver cells more vulnerable to toxicity and inflammation caused by bile acids.     <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>In this regard, the research team refers that, &#8220;the <em>in vivo<\/em> findings with bile duct blockade (BDL) were reproduced <em>in vitro<\/em> in primary mouse hepatocytes cultured with pharmacological depletion of mitochondrial GSH, which unmasked their sensitivity to BA-induced cytotoxicity and inflammation, as well as DNA damage revealed by comet tail length.&#8221; Thus, &#8220;our findings identify a previously unrecognized role for Stard1 in cholestasis and suggest that targeting Stard1 may be a novel approach for EHC,&#8221; they conclude. <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p><strong>HEVEPHARM, Group of Excellence of Castilla y Le\u00f3n<\/strong><\/p>\n\n<p>The Laboratory of Experimental Hepatology and Drug Vectorization (HEVEPHARM) is a multidisciplinary team led by Professor Jos\u00e9 Juan Garc\u00eda Mar\u00edn of the University of Salamanca and is composed of members of the Departments of Physiology and Pharmacology and Biochemistry and Molecular Biology of the University of Salamanca and the University Hospital of Salamanca.<\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>The group is attached to the Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL) and belongs to the Centro Nacional de Investigaci\u00f3n Biom\u00e9dica en Red para el Estudio de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD) of the Instituto de Salud Carlos III.<\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>Several of its members are members of the Spanish (AEEH) and European (EASL) Associations for the Study of the Liver, the Spanish Society of Biochemistry and Molecular Biology (SEBBM), the Spanish (SECF), British (PS) and American (APS) Societies of Physiology, the American Society for Pharmacology and Experimental Therapeutics (ASPET) and the Federation of American Societies for Experimental Biology (FASEB).<\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p>During the last 15 years the research group, recognized as a Group of Excellence of Castilla y Le\u00f3n, has been dedicated to the study of issues related to the biochemistry, physiology, physiopathology and pharmacology of the liver.<\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/saladeprensa.usal.es\/filessp\/atoms\/image\/higado-INT.jpeg\" alt=\"\"\/><\/figure>\n\n<p>Jos\u00e9 Juan Garc\u00eda Mar\u00edn (bottom left) with his HEVEPHARM team (USAL-IBSAL) and Jos\u00e9 C. Fern\u00e1ndez-Checa leading his group (IIB-CSIC-IDIBAPS).  <\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p><strong>Article reference:<\/strong><\/p>\n\n<p>Conde de la Rosa L, F\u00e1brega L, Torres S, Nu\u00f1ez S, Ribas V, Segal\u00e9s P, Espinosa-Escudero R, Solsona E, Monte MJ, Diaz-Gonzalez A, Marin JJG, Garc\u00eda-Ruiz C, Fernandez-Checa JC. <em>Stard1 promotes cholestatic liver injury and disease progression by sensitizing to bile acid hepatotoxicity<\/em>. HEPATOLOGY 2024 Dec 9.   <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39652774\/\" target=\"_blank\" rel=\"noreferrer noopener\">doi: 10.1097\/HEP.0000000000001184.<\/a><\/p>\n\n<div style=\"height:25px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n<p><strong>More information and contact:<\/strong><br\/><a href=\"mailto:jjgmarin@usal.es\">jjgmarin@usal.es<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The work is led by Jos\u00e9 Juan Garc\u00eda Mar\u00edn (USAL-IBSAL) and Jos\u00e9 C. Fern\u00e1ndez-Checa (IIBB-CSIC-IDIBAPS-), both from the Hepatic and Digestive Diseases area of the CIBER (CIBEREHD). Hepatology&#8217; reports the [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":6426,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_price":"","_stock":"","_tribe_ticket_header":"","_tribe_default_ticket_provider":"","_tribe_ticket_capacity":"0","_ticket_start_date":"","_ticket_end_date":"","_tribe_ticket_show_description":"","_tribe_ticket_show_not_going":false,"_tribe_ticket_use_global_stock":"","_tribe_ticket_global_stock_level":"","_global_stock_mode":"","_global_stock_cap":"","_tribe_rsvp_for_event":"","_tribe_ticket_going_count":"","_tribe_ticket_not_going_count":"","_tribe_tickets_list":"[]","_tribe_ticket_has_attendee_info_fields":false,"footnotes":""},"categories":[238],"tags":[244],"class_list":["post-6761","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-metabolism"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v20.12 (Yoast SEO v27.3) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Key role of Stard1 protein discovered in cholestatic liver diseases | IBSAL<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibsal.es\/en\/key-role-of-stard1-protein-discovered-in-cholestatic-liver-diseases\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Key role of Stard1 protein discovered in cholestatic liver diseases\" \/>\n<meta property=\"og:description\" content=\"The work is led by Jos\u00e9 Juan Garc\u00eda Mar\u00edn (USAL-IBSAL) and Jos\u00e9 C. 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