Indole-3-carbinol inhibits hepatic stellate cells proliferation by blocking NADPH oxidase/reactive oxygen species/p38 MAPK pathway.
During the course of liver fibrogenesis, hepatic stellate cell (HSC) proliferation as well as subsequent synthesis of excessive extracellular matrix components is known to be the central events. Thus, factors that could limit HSC proliferation are potential anti-fibrotic agents. The aim of this study was to investigate the effects of indole-3-carbinol (I3C), a nutritional component derived from Brassica family vegetables, on the proliferation of cultured HSC and to clarify the underline molecular mechanism. HSC-T6, an activated rat HSC line, was treated with I3C (50, 100 and 200 μM) for 24 h. The results indicated that I3C can significantly inhibit HSC proliferation in a concentration-dependent manner with or without platelet-derived growth factor-BB (PDGF-BB) stimulation (P<0.01). I3C could also block HSC in the G(0)/G(1) phase from entering the S phase. The expressions of α-smooth muscle actin in HSC treated with I3C, were significantly decreased at levels of protein and mRNA (P<0.01). In addition, the type I collagen level, cyclin D(1) and cyclin-dependent kinase 4 mRNA expressions, intracellular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and reactive oxygen species generation were significantly decreased by I3C (P<0.05). We also observed that the phosphorylated p38 MAPK in HSC-T6 was inhibited by I3C in a concentration-dependent manner; however, the phosphorylated ERK1/2 was unaltered. In conclusion, I3C could inhibit the proliferation of HSC by blocking the NADPH oxidase/reactive oxygen species/p38 MAPK signal pathway. These findings suggest that dietary I3C might play a novel role in prevention and treatment of chronic liver diseases.
Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan 430071, China.
Jie
J
Ping
Jing-ting
JT
Li
Zhang-xiu
ZX
Liao
Liang
L
Shang
Hui
H
Wang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007211:Indoles; D010982:Platelet-Derived Growth Factor; D017382:Reactive Oxygen Species; C016517:indole-3-carbinol; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases