Anti-fibrotic effects of tetrandrine on bile-duct ligated rats

2006 ◽  
Vol 84 (10) ◽  
pp. 967-976 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Yung-Tsung Chiu ◽  
Chang-Yin Lee ◽  
Ching-Fen Wu ◽  
Yi-Tsau Huang
Keyword(s):  
Bile Duct ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Smooth Muscle Actin ◽  
Intercellular Adhesion Molecule ◽  
Expression Levels ◽  
Metallothionein Gene ◽  
Duct Ligation ◽  
Tgf Β1 ◽  
Mrna Expression Levels

Tetrandrine (Tet) (C38H42O8N2; molecular weight, 622), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to elicit anti-inflammatory and anti-fibrotic effects in pulmonary diseases, but the mechanism of action has yet to be investigated. In this study, we tested whether Tet exerts anti-fibrotic effects on rat hepatic fibrosis through anti-NFκB pathways. After bile-duct ligation, rats were given Tet (1 or 5 mg/kg) or silymarin (50 mg/kg, as a positive control) by gavage twice daily for 3 weeks. Liver sections were taken for Sirius red quantitative scoring, immunofluorescence double staining of α-smooth muscle actin (α-SMA) and NFκB, and for quantitative determinations of the mRNA expression levels of TGF-β1, α-SMA, collagen 1α2, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), metallothionein, vascular endothelial growth factor (VEGF), and VEGF type II receptor (VEGFR2) genes. The results showed that both Tet and silymarin treatment significantly reduced the fibrosis scores and hepatic collagen content of BDL rats, compared with no treatment. Both Tet and silymarin treatments decreased the number of α-SMA- and NFκB-positive cells in fibrotic livers. Moreover, Tet and silymarin treatments attenuated the mRNA expression levels of TGF-β1,α-SMA, collagen 1α2, iNOS, ICAM-1, VEGF, and VEGFR2 genes, and induced the mRNA expression of the metallothionein gene. This study suggests that the anti-fibrotic effects of Tet were related to the reduction of fibrosis-related gene transcription, the attenuation of NFκB-activated pathways, and the induction of metallothionein gene transcription in the livers of BDL rats.

scholarly journals Effects of Ethyl Pyruvate on Bile Duct Ligation-Induced Liver Fibrosis by Regulating Nrf2 Pathway and Proinflammatory Cytokines in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yonghua Zong ◽  
Mingxiao Zhang ◽  
Shuai Li ◽  
Wenqian Qi ◽  
Juan Li ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Bile Duct Ligation ◽  
Ethyl Pyruvate ◽  
Antioxidant Genes ◽  
Duct Ligation ◽  
Nrf2 Signaling Pathway ◽  
Mrna Expression Levels

Aim. The aim of this paper is to investigate the effects of ethyl pyruvate (EP) on experimental liver fibrosis induced by bile duct ligation (BDL) and explore the underlying molecular mechanisms. Material and Method. Rats were randomly divided into three groups: the sham group, the BDL group, and the BDL+EP group. Liver fibrosis was induced by common bile duct ligation and was evaluated by serum biochemical parameter levels, Masson’s trichrome staining, α-SMA expression, and collagen I deposition. The levels of Nrf2 signaling pathway-related antioxidant genes (Nrf2, SOD2, NQO1, and GSH-Px) in liver tissues were also measured. Meanwhile, the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27 were analyzed. In BDL-induced liver fibrosis rats, the successfully established model was confirmed by the significant increase of serum ALT and AST levels, the high liver fibrosis score, α-SMA expression, and collagen deposition. Results. Compared with the BDL group, EP administration could diminish fibrosis level and substantially increase the expression of Nrf2 signaling pathway-related antioxidant genes. Furthermore, EP significantly suppressed the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27. Conclusions. The results suggested that EP administration could effectively inhibit the liver fibrosis induced by BDL in rat, which may be associated with the enhanced activity of Nrf2 to mediate antioxidant enzyme system and downregulate the inflammatory genes.

Protein and mRNA expression levels of VEGF-A and TGF-β1 in different types of human coronary atherosclerotic lesions

2005 ◽  
Author(s):  
Dimitrios Panutsopulos ◽  
Efstathios Papalambros ◽  
Fragiska Sigala ◽  
Alexandros Zafiropoulos ◽  
Dimitrios Arvanitis ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Levels ◽  
Atherosclerotic Lesions ◽  
Different Types ◽  
Tgf Β1 ◽  
Mrna Expression Levels

scholarly journals In vivo silencing of amphiregulin by a novel effective Self-Assembled-Micelle inhibitory RNA ameliorates renal fibrosis via inhibition of EGFR signals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung Seob Son ◽  
Soohyun Hwang ◽  
Jun Hong Park ◽  
Youngho Ko ◽  
Sung-Il Yun ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Adhesion Molecule ◽  
Renal Fibrosis ◽  
Smooth Muscle Actin ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Kidney Fibrosis ◽  
Self Assembled ◽  
Tgf Β1

AbstractAmphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.

scholarly journals High-trans fatty acid and high-sugar diets can cause mice with non-alcoholic steatohepatitis with liver fibrosis and potential pathogenesis

2020 ◽  
Author(s):  
Xin Xin ◽  
Bei-yu Cai ◽  
Cheng Chen ◽  
Hua-jie Tian ◽  
Xin Wang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Model Group ◽  
Expression Levels ◽  
Alcoholic Steatohepatitis ◽  
Tgf Β1 ◽  
Mrna Expression Levels ◽  
Liver Tissues

Abstract Aims To establish a mouse model of non-alcoholic steatohepatitis (NASH) within liver fibrosis using a high-fat and high-carbohydrate diet (HFHC) and to analyze potential pathogenesis using a transcriptome microarray. Methods Sixty mice were stratified by weight and randomly divided into HFHC model and control (Con) groups, with 30 mice in each group. Both HFHC and Con mice were euthanized at 0, 20 and 30 weeks. The following analyses were performed: biochemical analysis; histological assessment; Col-I, α-SMA and TGF-β1 protein and mRNA expression levels; and transcriptomic gene chip analysis. Results Compared with the Con group at each time point, the body weight and liver wet weight of the HFHC model group mice were significantly higher. At 30 weeks, ALT, AST, FBG and FINS levels or activities and TG and HYP contents in the HFHC model group were significantly elevated. Severe steatosis was present in the liver tissues from HFHC group mice. Substantial perisinusoidal fibrosis with a cage-like structure and bridging formations were observed in the liver. Col-I, α-SMA and TGF-β1 protein and mRNA expression levels in liver tissues from HFHC mice increased over time. Compared with the Con group, the HFHC group had 151 differentially expressed genes that were involved in 41 signaling pathways. Conclusions After 30 weeks of a HFHC diet, the mice exhibited substantial liver fibrosis, hepatic steatosis, ballooning degeneration and inflammation. The formation of an experimental NASH combined with liver fibrosis mouse model may be related to ECM-receptor interaction, Toll-like receptor signaling and other signaling pathways.

scholarly journals High-trans fatty acid and high-sugar diets can cause mice with non-alcoholic steatohepatitis with liver fibrosis and potential pathogenesis

2020 ◽  
Author(s):  
Xin Xin ◽  
Bei-yu Cai ◽  
Cheng Chen ◽  
Hua-jie Tian ◽  
Xin Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Fibrosis ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Model Group ◽  
Expression Levels ◽  
Alcoholic Steatohepatitis ◽  
Tgf Β1 ◽  
Mrna Expression Levels ◽  
Liver Tissues

Abstract Background and Aims: Even Non-alcoholic steatohepatitis (NASH) has been becoming the key role in process of liver fibrosis or cirrhosis, no any NASH involving liver fibrosis mice model which consistent with the mechanisms of fatty acid and glucose metabolism disorder was widely accepted. Here, we established a mouse model of nonalcoholic steatohepatitis (NASH) with liver fibrosis using a high-fat, high-carbohydrate diet (HFHC) and analyzed the potential pathogenesis using a transcriptome microarray. Methods: Fifty mice were stratified by weight and randomly divided into the HFHC model and control (Con) groups. 10 mice were sacrificed at the beginning of the experiments, 10 mice of HFHC and Con group were euthanized at the end of 20 and 30weeks. The following analyses were performed: biochemical analysis; histological assessment; evaluation of hepatic type I collagen (Col-I), α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) protein and mRNA expression levels; and transcriptomic gene chip analysis. Results: Compared with the Con group at each time point, the body weight and liver wet weight of the HFHC model group of mice were significantly higher. At 30th weeks, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG) and fasting insulin (FINS) levels or activities and the triglyceride (TG) and hydroxyproline (HYP) content in the HFHC model group were significantly elevated. Severe steatosis was present in the liver tissues contributed from the HFHC group of mice. Typically, substantial perisinusoidal fibrosis with a cage-like structure and bridging formations were observed in the mice liver in HFHC group. Col-I, α-SMA and TGF-β1 protein and mRNA expression levels in liver tissues of HFHC mice dramatically increased over time. Compared with the Con group, the HFHC group had 151 differentially expressed genes that were involved in 41 signaling pathways. Conclusions: After keeping 30 weeks HFHC diet treatment, the mice exhibited substantial liver fibrosis, hepatic steatosis, ballooning degeneration and inflammation. Basing on the transcriptome microarray assays, the experimental NASH involving liver fibrosis potentially related to dramatically changed ECM-receptor interaction, Toll-like receptor signaling and other signaling pathways.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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