Effect of Yiguanjian decoction on cell differentiation and proliferation in CCl₄-treated mice.
OBJECTIVE
To investigate the cellular mechanisms of action of Yiguanjian (YGJ) decoction in treatment of chronic hepatic injury.


METHODS
One group of mice was irradiated, and received enhanced green fluorescent protein (EGFP)-positive bone marrow transplants followed by 13 wk of CCl₄ injection and 6 wk of oral YGJ administration. A second group of Institute for Cancer Research mice was treated with 13 wk of CCl₄ injection and 6 wk of oral YGJ administration. Liver function, histological changes in the liver, and Hyp content were analyzed. The expression of α-smooth muscle actin (α-SMA), F4/80, albumin (Alb), EGFP, mitogen-activated protein kinase-2 (PKM2), Ki-67, α fetoprotein (AFP), monocyte chemotaxis protein-1 and CC chemokine receptor 2 were assayed.


RESULTS
As hepatic damage progressed, EGFP-positive marrow cells migrated into the liver and were mainly distributed along the fibrous septa. They showed a conspicuous coexpression of EGFP with α-SMA and F4/80 but no coexpression with Alb. Moreover, the expression of PKM2, AFP and Ki-67 was enhanced dynamically and steadily over the course of liver injury. YGJ abrogated the increases in the number of bone marrow-derived fibrogenic cells in the liver, inhibited expression of both progenitor and mature hepatocyte markers, and reduced fibrogenesis.


CONCLUSIONS
YGJ decoction improves liver fibrosis by inhibiting the migration of bone marrow cells into the liver as well as inhibiting their differentiation and suppressing the proliferation of both progenitors and hepatocytes in the injured liver.
Department of Cell Biology, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 210203, China.
Xiao-Ling
XL
Wang
Dong-Wei
DW
Jia
Hui-Yang
HY
Liu
Xiao-Feng
XF
Yan
Ting-Jie
TJ
Ye
Xu-Dong
XD
Hu
Bo-Qin
BQ
Li
Yong-Liang
YL
Chen
Ping
P
Liu
D000199:Actins / Q000378:metabolism; D000284:Administration, Oral; D000418:Albumins / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000378:metabolism
D000199:Actins; D000418:Albumins; D000943:Antigens, Differentiation; D015415:Biomarkers; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D004365:Drugs, Chinese Herbal; D019394:Ki-67 Antigen; D054390:Receptors, CCR2; D000509:alpha-Fetoproteins; C544013:alpha-smooth muscle actin, mouse; C485184:enhanced green fluorescent protein; C036763:monocyte-macrophage differentiation antigen; C576320:yiguanjian decoction; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1