Nicotinamide induces apoptosis and reduces collagen I and pro-inflammatory cytokines expression in rat hepatic stellate cells

2005 ◽  
Vol 40 (10) ◽  
pp. 1226-1234 ◽  
Author(s):  
Alexandra Traister ◽  
Igal Breitman ◽  
Ella Bar-Lev ◽  
Isabel Zvibel ◽  
Avikam Harel ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Collagen I ◽  
Pro Inflammatory Cytokines

Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells

2014 ◽  
Vol 306 (3) ◽  
pp. G253-G263 ◽  
Author(s):  
Yu Peng ◽  
Huixiang Yang ◽  
Nasui Wang ◽  
Yan Ouyang ◽  
Yanrong Yi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Fibrosis ◽  
Western Blot ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Cyclin E ◽  
Stellate Cells ◽  
Collagen I ◽  
Phase Cell ◽  
Cyclin D

Fluorofenidone (AKF-PD) is a novel pyridone agent. The purpose of this study is to investigate the inhibitory effects of AKF-PD on liver fibrosis in rats and the involved molecular mechanism related to hepatic stellate cells (HSCs). Rats treated with dimethylnitrosamine or CCl4 were randomly divided into normal, model, AKF-PD treatment, and pirfenidone (PFD) treatment groups. The isolated primary rat HSCs were treated with AKF-PD and PFD respectively. Cell proliferation and cell cycle distribution were analyzed by bromodeoxyuridine and flow cytometry, respectively. The expression of collagen I and α-smooth muscle actin (α-SMA) were determined by Western blot, immunohistochemical staining, and real-time RT-PCR. The expression of cyclin D1, cyclin E, and p27kip1 and phosphorylation of MEK, ERK, Akt, and 70-kDa ribosomal S6 kinase (p70S6K) were detected by Western blot. AKF-PD significantly inhibited PDGF-BB-induced HSC proliferation and activation by attenuating the expression of collagen I and α-SMA, causing G0/G1 phase cell cycle arrest, reducing expression of cyclin D1 and cyclin E, and promoting expression of p27kip1. AKF-PD also downregulated PDGF-BB-induced MEK, ERK, Akt, and p70S6K phosphorylation in HSCs. In rat liver fibrosis, AKF-PD alleviated hepatic fibrosis by decreasing necroinflammatory score and semiquantitative score, and reducing expression of collagen I and α-SMA. AKF-PD attenuated the progression of hepatic fibrosis by suppressing HSCs proliferation and activation via the ERK/MAPK and PI3K/Akt signaling pathways. AKF-PD may be used as a potential novel therapeutic agent against liver fibrosis.

scholarly journals miR-21 promotes α-SMA and collagen I expression in hepatic stellate cells via the Smad7 signaling pathway

2017 ◽  
Vol 16 (4) ◽  
pp. 4327-4333 ◽  
Author(s):  
Rong-Quan Fu ◽  
Dan-Ping Hu ◽  
Yi-Bing Hu ◽  
Liang Hong ◽  
Qing-Feng Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Collagen I

scholarly journals CXCL6 promotes human hepatocyte proliferation through the CXCR1–NFκB pathway and inhibits collagen I secretion by hepatic stellate cells

2016 ◽  
Vol 94 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Zhenghong Li ◽  
Qidi Zhang ◽  
Qingqing Zhang ◽  
Mingyi Xu ◽  
Ying Qu ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Alanine Transaminase ◽  
Collagen I ◽  
Hepatocyte Proliferation ◽  
Aspartate Transaminase ◽  
Nfκb Pathway ◽  
L02 Cells

Hepatocyte proliferation and collagen I (COLI) secretion are important processes during liver regeneration. This study aimed to investigate the role of CXCL6 in hepatocyte proliferation and COLI secretion. Serum CXCL6 levels in patients with chronic hepatitis B (CHB) were examined and the effects of CXCL6 on the proliferation of L02 hepatocytes and the secretion of COLI from LX2 human hepatic stellate cells were evaluated. We found that serum CXCL6 levels increased gradually with disease progression of CHB, and there was positive correlation between serum CXCL6 level and alanine transaminase (ALT) and aspartate transaminase (AST). In vitro, CXCL6 promoted L02 proliferation but this was blocked upon CXCR1 knockdown. The level of phospho-IκBα was upregulated by CXCL6 but downregulated by CXCR1 siRNA in L02 cells. CXCL6 inhibited the secretion of COLI by LX2 cells, dependent on CXCR1 and CXCR2. Taken together, these data suggest that increased expression of CXCL6 during CHB could promote hepatocyte proliferation through the CXCR1–NFκB pathway and inhibit the secretion of COLI by hepatic stellate cells.

scholarly journals The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism

2013 ◽  
Vol 33 (3) ◽  
Author(s):  
Tianhui Liu ◽  
Ping Wang ◽  
Min Cong ◽  
Youqing Xu ◽  
Jidong Jia ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Matrix Metalloproteinase ◽  
Hepatic Stellate Cells ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Collagen I ◽  
Akt Inhibitor ◽  
H2o2 Treatment ◽  
P38 Inhibitor ◽  
Matrix Metalloproteinase 1

DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis.

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