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WebPage:
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         headline:Ruxolitinib suppresses liver fibrosis progression and accelerates fibrosis reversal via selectively targeting Janus kinase 1/2
         description:JAK1 and JAK2 have been implicated in fibrosis and cancer as a fibroblast-related marker; however, their role in liver fibrosis has not been elucidated. Here, we aim to determine the effect and underlying mechanism of JAK1/2 inhibition on liver fibrosis and hepatic stellate cells (HSCs) and further explore the therapeutic efficacy of Ruxolitinib, a JAK1/2 selective inhibitor, on preventing and reversing liver fibrosis in mice. Immunohistochemistry staining of JAK1 and JAK2 were performed on liver tissue in mice with hepatic fibrosis and human liver tissue microarray of liver cirrhosis and liver cancer. LX-2 cells treated with specific siRNA of JAK1 and JAK2 were used to analysis activation, proliferation and migration of HSCs regulated by JAK1/2. The effects of Ruxolitinib (JAK1/2 inhibitor) on liver fibrosis were studied in LX-2 cells and two progressive and reversible fibrosis animal models (carbon tetrachloride (CCl4), Thioacetamide (TAA)). We found that JAK1/2 expression was positively correlated with the progression of HCC in humans and the levels of liver fibrosis in mice. Silencing of JAK1/2 down-regulated their downstream signaling and inhibited proliferation, migration, and activation of HSCs in vitro, while Ruxolitinib had similar effects on HSCs. Importantly, Ruxolitinib significantly attenuated fibrosis progression, improved cell damage, and accelerated fibrosis reversal in the liver of mice treated with CCl4 or TAA. JAK1/2 regulates the function of HSCs and plays an essential role in liver fibrosis and HCC development. Its inhibitor, Ruxolitinib, may be an effective drug for preventing and treating liver fibrosis.
         datePublished:2022-04-05T00:00:00Z
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            Janus Kinase 2
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      headline:Ruxolitinib suppresses liver fibrosis progression and accelerates fibrosis reversal via selectively targeting Janus kinase 1/2
      description:JAK1 and JAK2 have been implicated in fibrosis and cancer as a fibroblast-related marker; however, their role in liver fibrosis has not been elucidated. Here, we aim to determine the effect and underlying mechanism of JAK1/2 inhibition on liver fibrosis and hepatic stellate cells (HSCs) and further explore the therapeutic efficacy of Ruxolitinib, a JAK1/2 selective inhibitor, on preventing and reversing liver fibrosis in mice. Immunohistochemistry staining of JAK1 and JAK2 were performed on liver tissue in mice with hepatic fibrosis and human liver tissue microarray of liver cirrhosis and liver cancer. LX-2 cells treated with specific siRNA of JAK1 and JAK2 were used to analysis activation, proliferation and migration of HSCs regulated by JAK1/2. The effects of Ruxolitinib (JAK1/2 inhibitor) on liver fibrosis were studied in LX-2 cells and two progressive and reversible fibrosis animal models (carbon tetrachloride (CCl4), Thioacetamide (TAA)). We found that JAK1/2 expression was positively correlated with the progression of HCC in humans and the levels of liver fibrosis in mice. Silencing of JAK1/2 down-regulated their downstream signaling and inhibited proliferation, migration, and activation of HSCs in vitro, while Ruxolitinib had similar effects on HSCs. Importantly, Ruxolitinib significantly attenuated fibrosis progression, improved cell damage, and accelerated fibrosis reversal in the liver of mice treated with CCl4 or TAA. JAK1/2 regulates the function of HSCs and plays an essential role in liver fibrosis and HCC development. Its inhibitor, Ruxolitinib, may be an effective drug for preventing and treating liver fibrosis.
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      dateModified:2022-04-05T00:00:00Z
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         Janus Kinase 1
         Janus Kinase 2
         Liver Fibrosis
         HSCs
         Ruxolitinib
         Biomedicine
         general
         Medicine/Public Health
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      email:[email protected]
      name:Aimin Li
      url:http://orcid.org/0000-0001-9459-5540
      affiliation:
            name:Southern Medical University
            address:
               name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
            name:Southern Medical University
            address:
               name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
            name:Michigan State University
            address:
               name:Department of Physiology, Michigan State University, East Lansing, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:Department of Physiology, Michigan State University, East Lansing, USA
      name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:Department of Physiology, Michigan State University, East Lansing, USA
      name:Department of Physiology, Michigan State University, East Lansing, USA
      name:Department of Endocrinology and Metabolic Diseases, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, China
      name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Medicine, Jinan University, Guangzhou, China
      name:Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
      name:Department of Physiology, Michigan State University, East Lansing, USA

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