TY - JOUR
T1 - Modulation of HIF-1α and STAT3 signaling contributes to antiangiogenic effect of YC-1 in mice with liver fibrosis
AU - Lee, Tzung Yan
AU - Leu, Yann Lii
AU - Wen, Chorng Kai
N1 - Publisher Copyright:
© Lee et al.
PY - 2017/10/17
Y1 - 2017/10/17
N2 - Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The aim of the study was to evaluate the mechanisms of HIF-1α inhibitor, YC-1, during bile duct ligation (BDL)-induced liver fibrosis in mice. Liver fibrosis was induced in mice, and YC-1 was then given intraperitoneally (50 mg/kg) once daily following 5 days. Liver injuries mice that were treated with YC-1 showed improved inflammatory response and diminished angiogenesis and hepatic fibrosis. YC-1 treatment inhibited liver neutrophil infiltration, while a decreased in TNF-α signaling as well as macrophage aggregation. In addition, YC-1 downregulates iNOS and COX-2 levels by inhibiting the activation of NF-κB and STAT3 phosphorylation by negative regulation the expression of SOCS1 and SOCS3 signaling. On the other hand, YC-1 decreased angiogenesis, as shown by the downregulation of hypoxiainducible cascade genes, i.e. VEGF. YC-1 treatment resulted in a significant decrease in hepatic fibrogenesis, α-SMA abundance, and TGF-βR1 expression as well as hypoxia were assessed using VEGFR1, vWF and HIF-1α immunostaining. These results suggest that multi-targeted therapies directed against angiogenesis, hypoxia, and fibrosis. Therefore, it may be suggested that YC-1 treatment may be a novel therapeutic agent for the treatment of liver disease.
AB - Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The aim of the study was to evaluate the mechanisms of HIF-1α inhibitor, YC-1, during bile duct ligation (BDL)-induced liver fibrosis in mice. Liver fibrosis was induced in mice, and YC-1 was then given intraperitoneally (50 mg/kg) once daily following 5 days. Liver injuries mice that were treated with YC-1 showed improved inflammatory response and diminished angiogenesis and hepatic fibrosis. YC-1 treatment inhibited liver neutrophil infiltration, while a decreased in TNF-α signaling as well as macrophage aggregation. In addition, YC-1 downregulates iNOS and COX-2 levels by inhibiting the activation of NF-κB and STAT3 phosphorylation by negative regulation the expression of SOCS1 and SOCS3 signaling. On the other hand, YC-1 decreased angiogenesis, as shown by the downregulation of hypoxiainducible cascade genes, i.e. VEGF. YC-1 treatment resulted in a significant decrease in hepatic fibrogenesis, α-SMA abundance, and TGF-βR1 expression as well as hypoxia were assessed using VEGFR1, vWF and HIF-1α immunostaining. These results suggest that multi-targeted therapies directed against angiogenesis, hypoxia, and fibrosis. Therefore, it may be suggested that YC-1 treatment may be a novel therapeutic agent for the treatment of liver disease.
KW - Angiogenesis
KW - Fibrosis
KW - Hypoxia-inducible factor-1α
KW - Inflammation
KW - YC-1
UR - http://www.scopus.com/inward/record.url?scp=85031493514&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.21039
DO - 10.18632/oncotarget.21039
M3 - 文章
C2 - 29156788
AN - SCOPUS:85031493514
SN - 1949-2553
VL - 8
SP - 86206
EP - 86216
JO - Oncotarget
JF - Oncotarget
IS - 49
ER -