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10.1038/cddis.2017.99

http://scihub22266oqcxt.onion/10.1038/cddis.2017.99
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C5386589!5386589!28358366
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suck abstract from ncbi


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pmid28358366      Cell+Death+Dis 2017 ; 8 (3): e2719-
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  • Forkhead box A3 attenuated the progression of fibrosis in a rat model of biliary atresia #MMPMID28358366
  • Dong R; Yang Y; Shen Z; Zheng C; Jin Z; Huang Y; Zhang Z; Zheng S; Chen G
  • Cell Death Dis 2017[Mar]; 8 (3): e2719- PMID28358366show ga
  • Biliary atresia is a rare, devastating disease of infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and death if untreated. The cause and pathogenesis remain largely unknown. We tried to investigate factors involved in biliary atresia, especially forkhead box A3 (Foxa3), which might exert a role in the treatment of liver disease. We used RNA sequencing to sequence the whole transcriptomes of livers from six biliary atresia and six choledochal cysts patients. Then, we employed a rat disease model by bile duct ligation (BDL) and adenovirus transduction to address the function of Foxa3 in biliary atresia. We found that tight junction, adherence junction, cell cycle, apoptosis, chemokine singling, VEGF and MAPK signaling pathways were enriched in biliary atresia livers. We showed that Foxa3 expression was notably decreased in liver samples from biliary atresia patients. More importantly, we found that its lower expression predicted a poorer overall survival of biliary atresia patients. Rats that received BDL surgery and Foxa3 expression adenovirus resulted in a significant decrease in the deposition of collagen, and expression of profibrotic cytokines (transforming growth factor-? and connective tissue growth factor) and fibrosis markers (?-smooth muscle actin, collagen I and collagen III), as compared with rats that received BDL surgery and control adenovirus. Our data suggested a protection role for Foxa3 during the progression of liver fibrosis in biliary atresia, and thereby supported increasing Foxa3 as a targeted treatment strategy.
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