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Autophagy regulates hepatocellular senescence
Author(s) -
Huda Nazmul,
Khambu Bilon,
Chen Xiaoyun,
Yin XiaoMing
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.470.1
Subject(s) - autophagy , senescence , hepatocyte , microbiology and biotechnology , biology , phenotype , oxidative stress , cancer research , in vitro , apoptosis , endocrinology , genetics , gene
Autophagy and senescence are two distinct but functionally intertwined stress mediated cellular process. In advanced human liver disease there is widespread senescence in hepatocytes. Several lines of evidence showed that the hepatocyte senescence was associated closely with fibrosis stage and an adverse outcome in chronic liver disease. Mechanism that establishes the relationship between autophagy and senescence in liver is unclear. In this study we have used mice whose hepatocytes lack Atg7 (and thus autophagy) to elucidate the precise trigger that induce senescence and the pathway leading to senescence mechanism. Here we report evidence that autophagy deficient hepatocytes showed higher expression of senescence associated factors including p15, p21, CDKN3, & HP1 γ compared to wildtype. Autophagy defects activated the oxidative stress and DNA damage responses in hepatocytes. Moreover, the autophagy deficiency caused significantly increase in β‐galactosidase activity, and SASP phenotype in hepatocytes. Conclusion Dysregulation of autophagy causes senescence in hepatocytes, which can contribute to the pathology of the autophagy‐deficient liver. Support or Funding Information NIH, R21AA 021450 and R01AA021751; Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis, IN 46202