Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10901510 | Cancer Letters | 2016 | 10 Pages |
Abstract
Autophagy is a highly conserved and lysosome-dependent degradation process which assists in cell survival and tissue homeostasis. Although previous reports have shown that deletion of the essential autophagy gene disturbs stem cell maintenance in some cell types such as hematopoietic and neural cells, it remains unclear how autophagy-deficiency influences hepatic progenitor cells (HPCs). Here we report that Atg5-deficiency in HPCs delays HPC-mediated rat liver regeneration in vivo. In vitro researches further demonstrate that loss of autophagy decreases the abilities of colony and spheroid formations, and disrupts the induction of hepatic differentiation in HPCs. Meanwhile, autophagy-deficiency increases the accumulations of damaged mitochondria and mitochondrial reactive oxygen species (mtROS) and suppresses homologous recombination (HR) pathway of DNA damage repair in HPCs. Moreover, in both diethylnitrosamine (DEN) and CCl4 models, autophagy-deficiency accelerates neoplastic transformation of HPCs. In conclusion, these findings demonstrate that autophagy contributes to stemness maintenance and reduces susceptibility to neoplastic transformation in HPCs.
Keywords
SPCsHSCsDenγ-H2AX8-OHdGALTG6Pi.pNHEJDSBsALBshRNAMSRmtROSNSCsDNA-PKcsDMEMFBSCCK8qPCRTBIL8-Hydroxy-2-deoxyguanosineH&EHPCsDulbecco's modified Eagle's mediumshort hairpin RNAASTAspartate aminotransferaseAlanine aminotransferaseAlbuminAutophagyIonizing irradiationStemnessDNA damage repairNeoplastic transformationScrambleintraperitonealdiethylnitrosaminefetal bovine serumStem/progenitor cellshematopoietic stem cellshepatic progenitor cellsNeural stem cellscell counting kit-8double-strand breaksHematoxylin and Eosinphosphorylated histone H2AXDNA-dependent protein kinasequantitative real-time PCRNonhomologous end joiningtotal bilirubinglucose-6-phosphatasemitochondrial reactive oxygen speciesSCR
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Authors
Feng Xue, Lei Hu, Ruiliang Ge, Lixue Yang, Kai Liu, Yunyun Li, Yanfu Sun, Kui Wang,