{"id":8093,"date":"2015-12-07T13:45:49","date_gmt":"2015-12-07T21:45:49","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=8093"},"modified":"2015-12-07T17:41:14","modified_gmt":"2015-12-08T01:41:14","slug":"fighting-liver-fibrosis-the-wound-that-never-heals","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/fighting-liver-fibrosis-the-wound-that-never-heals\/","title":{"rendered":"Fighting liver fibrosis, the wound that never heals"},"content":{"rendered":"

LA JOLLA\u2014Chronic damage to the liver eventually creates a wound that never heals. This condition, called fibrosis, gradually replaces normal liver cells\u2014which detoxify the food and liquid we consume\u2014with more and more scar tissue until the organ no longer works.\n<\/p>\n

\nScientists at the Salk Institute have identified a drug that halts this unchecked accumulation of scar tissue in the liver. The small molecule, called JQ1, prevented as well as reversed fibrosis in animals and could help the millions of people worldwide affected by liver fibrosis and cirrhosis, caused by alcoholism and diseases like hepatitis. These results were published in PNAS<\/em> the week of December 7, 2015.\n<\/p>\n

\"\"

Liver cells in a dish (left) become scar tissue when exposed to carcinogens (center). The Salk team found that the molecule JQ1 blocks scarring in animals by preventing normal liver cells from changing into scar-producing cells (right).<\/p>\n

Credit: Salk Institute for Biological Studies
<\/figcaption><\/figure>\n

\n\u201cAfter too much damage in the liver, the scar tissue itself causes more scar tissue,\u201d says Ronald Evans<\/a>, professor and director of Salk\u2019s Gene Expression Laboratory and a Howard Hughes Medical Institute investigator. \u201cWe can actually reverse liver fibrosis in animals and are now exploring potential therapeutic applications for humans.\u201d\n<\/p>\n

\nWhen the liver is damaged, small collections of hepatic stellate cells that specialize in storing vitamin A are called upon to tend to the wound. These activated stellate cells shed their vitamin A, travel to the site of injury and create thick, fibrous scar tissue to wall off and repair the damage. However, with prolonged organ stress, healthy liver cells become replaced by scar tissue, eventually leading to organ failure.\n<\/p>\n

\n\u201cTraditional therapies targeting inflammation don\u2019t work because these cells have multiple ways to bypass the drug,\u201d says Michael Downes, a Salk senior scientist and author of the paper. \u201cIn contrast, our strategy was to stop the fibrotic response at the genome level where these pathways converge.\u201d\n<\/p>\n

\nThe search for the critical genome pathway struck gold, uncovering a regulatory protein, called BRD4, that is a master regulator of liver fibrosis.\n<\/p>\n

\"From
From left: Nasun Hah, Ruth Yu, Mara Sherman, Ron Evans, Michael Downes, Chris Liddle and Ann Atkins<\/p>\n

Click here for a high-resolution image»<\/a><\/p>\n

Bild: Mit freundlicher Genehmigung des Salk Institute for Biological Studies<\/figcaption><\/figure>\n

\nWith this new knowledge in hand, the Salk team found JQ1 successfully inhibited BRD4 and halted the transformation of hepatic stellate cells into fiber-producing cells. This is good news, as JQ1 is a prototype of a new class of drugs currently being tested in human clinical trials for various cancers.\n<\/p>\n

\n\u201cJQ1 doesn\u2019t just protect against the wound response, but also reverses the fibrotic response in mice,\u201d says Ruth Yu, a Salk staff researcher and one of the authors of the paper.\n<\/p>\n

\n\u201cOur results indicate that BRD4 is a driver of chronic fibrosis and a promising therapeutic target for treating liver disease,\u201d says Evans, who also holds the March of Dimes Chair in Molecular and Developmental Biology. \u201cWe think this discovery may also treat fibrosis in other organs, like the lung, pancreas and kidney.\u201d\n<\/p>\n

\nOther authors include Ning Ding, Nasun Hah, Mara Sherman, Chris Benner, Mathias Leblanc and Mingxiao He of the Salk Institute, and Christopher Liddle of the University of Sydney.\n<\/p>\n

\nThe work was funded by the NIH, the National Health and Medical Research Council of Australia Project Grants, the Leona M. and Harry B. Helmsley Charitable Trust, the Samuel Waxman Cancer Research Foundation and Ipsen\/Biomeasure.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[91],"disease-research":[146],"class_list":["post-8093","disclosure","type-disclosure","status-publish","hentry","faculty-ronald-evans","disease-research-aging-and-regenerative-medicine"],"acf":[],"yoast_head":"\nFighting liver fibrosis, the wound that never heals - Salk Institute for Biological Studies<\/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:\/\/www.salk.edu\/de\/news-release\/fighting-liver-fibrosis-the-wound-that-never-heals\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Fighting liver fibrosis, the wound that never heals - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Chronic damage to the liver eventually creates a wound that never heals. 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