The Roles of Activin A and B in Liver Inflammation and Fibrosis
type: CreativeWork
description: Liver fibrosis is the result of different types of chronic liver diseases, such as cholestatic liver disease and nonalcoholic steatohepatitis, among others. Fibrosis, if left unchecked, may progress to the point of cirrhosis – permanently affecting liver function detrimentally and potentially leading to development of hepatocellular carcinoma. Inflammatory response following tissue injury is vital for the initiation of fibrosis; chronic inflammation results in abnormal tissue healing and promotes a pro-fibrogenic response. Activins are cytokines that have been identified as members of the TGFβ superfamily of growth and differentiation factors. Activin A and B, in particular, have been identified as having roles in the pathophysiology of liver disease, but have not been investigated thoroughly. We treated mice with concanavalin A, a potent T-cell mitogen with liver specificity when administered intravenously, and characterized the resulting response to liver injury and how activin A and B are modulated during this acute inflammatory phase. We showed that activin B is highly increased in circulation following inflammation, as well as locally in the liver as well as the spleen. We then neutralized activin A and B via neutralizing antibodies in our concanavalin A-induced liver injury model to determine if inhibition of these ligands may confer protective effects during the acute inflammatory response in liver. Neutralization of either activin A or activin B protected hepatocytes, improved liver function, and significantly reduced circulating cytokines following concanavalin A administration. Finally, we determined whether inhibition of activin A or B might prevent or reverse the development of liver fibrosis after disease has been established. We induced liver fibrosis in mice via the hepatotoxin carbon tetrachloride, and then treated with neutralizing antibodies while still maintaining carbon tetrachloride administration. Neutralization of activin A and B markedly redu…
abstract: Liver fibrosis is the result of different types of chronic liver diseases, such as cholestatic liver disease and nonalcoholic steatohepatitis, among others. Fibrosis, if left unchecked, may progress to the point of cirrhosis – permanently affecting liver function detrimentally and potentially leading to development of hepatocellular carcinoma. Inflammatory response following tissue injury is vital for the initiation of fibrosis; chronic inflammation results in abnormal tissue healing and promotes a pro-fibrogenic response. Activins are cytokines that have been identified as members of the TGFβ superfamily of growth and differentiation factors. Activin A and B, in particular, have been identified as having roles in the pathophysiology of liver disease, but have not been investigated thoroughly. We treated mice with concanavalin A, a potent T-cell mitogen with liver specificity when administered intravenously, and characterized the resulting response to liver injury and how activin A and B are modulated during this acute inflammatory phase. We showed that activin B is highly increased in circulation following inflammation, as well as locally in the liver as well as the spleen. We then neutralized activin A and B via neutralizing antibodies in our concanavalin A-induced liver injury model to determine if inhibition of these ligands may confer protective effects during the acute inflammatory response in liver. Neutralization of either activin A or activin B protected hepatocytes, improved liver function, and significantly reduced circulating cytokines following concanavalin A administration. Finally, we determined whether inhibition of activin A or B might prevent or reverse the development of liver fibrosis after disease has been established. We induced liver fibrosis in mice via the hepatotoxin carbon tetrachloride, and then treated with neutralizing antibodies while still maintaining carbon tetrachloride administration. Neutralization of activin A and B markedly redu…
author: Hamang, Matthew J.
language: en_US
keywords: Activin, Inflammation, Liver fibrosis
date published: 2019-05
date modified: 2026-07-24T02:40:57Z
provider: IUPUI
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: IUPUI

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1805/19008

PropertyValue
property ID: DOI
value: 10.7912/C2/2210