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논문 기본 정보
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- 학술저널
- 저자정보
- 발행연도
- 2017.1
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Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage.
However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0.1% ethionine (MCDE) for 2 weeks were injected with TSG-6 (the M+TSG-6 group) or saline (the M+V group) and fed with MCDE for 2 additional weeks. Histomorphological evidence of injury and increased levels of liver enzymes were evident in MCDE-treated mice, whereas these symptoms were ameliorated in the M+TSG-6 group. Livers from this group contained less active caspase-3 and more Ki67-positive hepatocytic cells than the M+V group. The autophagy markers ATG3, ATG7, LC3-II, LAMP2A and RAB7 were elevated in the M+TSG-6 group compared with those in the M+V group. Immunostaining for LC3 and RAB7 and electron microscopy analysis showed the accumulation of autophagy structures in the M+TSG-6 group. TSG-6 also blocked both tunicamycin- and palmitate-induced apoptosis of hepatocytes and increased their viability by inducing autophagy formation in these cells. An autophagy inhibitor suppressed TSG-6-mediated autophagy in the injured hepatocytes and livers of MCDE-treated mice. These results therefore demonstrate that TSG-6 protects hepatocytes from damage by enhancing autophagy influx and contributes to liver regeneration, suggesting that TSG-6 has therapeutic potential for the treatment of liver diseases.
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참고문헌 (27)
참고문헌 신청
Chung C / 2012 / Activated hepatic stellate cells : negative regulators of hepatocyte proliferation in liver diseases / Hepatology 56 : 389 ~ 391
Czaja MJ / 2013 / Functions of autophagy in normal and diseased liver / Autophagy 9 : 1131 ~ 1158
Fausto N. / 2004 / Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells / Hepatology 39 : 1477 ~ 1487
Garcia-Martinez R / 2013 / Albumin : pathophysiologic basis of its role in the treatment of cirrhosis and its complications / Hepatology 58 : 1836 ~ 1846
Grompe M / 2013 / Mice with human livers / Gastroenterology 145 : 1209 ~ 1214
Czaja MJ / 2013 / Functions of autophagy in normal and diseased liver / Autophagy 9 : 1131 ~ 1158
Fausto N. / 2004 / Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells / Hepatology 39 : 1477 ~ 1487
Garcia-Martinez R / 2013 / Albumin : pathophysiologic basis of its role in the treatment of cirrhosis and its complications / Hepatology 58 : 1836 ~ 1846
Grompe M / 2013 / Mice with human livers / Gastroenterology 145 : 1209 ~ 1214
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