TY - JOUR
T1 - Microcystin-leucine-arginine induces liver fibrosis by activating the Hedgehog pathway in hepatic stellate cells
AU - Gu, Shen
AU - Yan, Minghao
AU - Wang, Cong
AU - Meng, Xiannan
AU - Xiang, Zou
AU - Qiu, Yudong
AU - Han, Xiaodong
N1 - Funding Information:
We thank Jun Chen, Xiang Chen, Yabin Chen and Mingxuemei Jiang for assistance. The authors declare they have no competing interests. This work was supported by the National Natural Science Foundation of China ( 31971518 and 31670519 ) and the Key Medical Subjects of Jiangsu Province ( ZDRCA2016057 ).
Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Microcystin-leucine-arginine (MC-LR), produced by cyanobacteria, accumulates in the liver through blood circulation. We investigated the impact of MC-LR on liver fibrosis. Mice received a daily injection of MC-LR at various concentrations for 14 consecutive days aa and then mouse liver was obtained for histopathological and immunoblot analysis. Next, a human hepatic stellate cell line (LX-2) was treated with MC-LR at various concentrations followed by measurement of cell viability, cell cycle and relevant protein expression levels. Our data confirmed the induction of mouse liver fibrosis after exposure to MC-LR at 15 μg/kg and 30 μg/kg. Furthermore, we demonstrated that LX-2 cells could uptake MC-LR, resulting in cell proliferation and differentiation through impacting the Hedgehog signaling after the treatment of MC-LR at 50 nM. Our data supported that MC- LR could induce liver fibrosis by modulating the expression of the transcription factor Gli2 in the Hedgehog signaling in hepatic stellate cells.
AB - Microcystin-leucine-arginine (MC-LR), produced by cyanobacteria, accumulates in the liver through blood circulation. We investigated the impact of MC-LR on liver fibrosis. Mice received a daily injection of MC-LR at various concentrations for 14 consecutive days aa and then mouse liver was obtained for histopathological and immunoblot analysis. Next, a human hepatic stellate cell line (LX-2) was treated with MC-LR at various concentrations followed by measurement of cell viability, cell cycle and relevant protein expression levels. Our data confirmed the induction of mouse liver fibrosis after exposure to MC-LR at 15 μg/kg and 30 μg/kg. Furthermore, we demonstrated that LX-2 cells could uptake MC-LR, resulting in cell proliferation and differentiation through impacting the Hedgehog signaling after the treatment of MC-LR at 50 nM. Our data supported that MC- LR could induce liver fibrosis by modulating the expression of the transcription factor Gli2 in the Hedgehog signaling in hepatic stellate cells.
KW - Gli
KW - Liver fibrosis
KW - Microcystin-leucine arginine
KW - The hedgehog signaling
UR - http://www.scopus.com/inward/record.url?scp=85091803440&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.09.075
DO - 10.1016/j.bbrc.2020.09.075
M3 - Journal article
AN - SCOPUS:85091803440
SN - 0006-291X
VL - 533
SP - 770
EP - 778
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -