TGF-β1 In Liver Tissues Research Articles

High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-β1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

The potential hepatoprotective effect of quercetin on cholestatic liver injury in rats

Abstract Background cholestasis is a prevalent health problem associated with liver oxidative stress, inflammation, and fibrosis. Quercetin has been shown to afford a beneficial effect in a variety of liver diseases. Aim This study was designed to investigate the potential protective effect of quercetin on liver cholestasis and the possible underlying mechanisms in a rat model of bile duct ligation (BDL). Design Experimental study Methods This study was carried out on adult male Wister rats which were randomly divided into: Sham, BDL and BDL- quercetin treated (BDL- Q) groups. Quercetin was given by gavage in a dose of 50 mg/kg/day. Results Bile duct ligation resulted in a significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and liver levels of myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α),and transforming growth factor beta 1(TGF-β1), along with a significant decrease in serum levels of total proteins (TP) and liver glutathione peroxidase(GPX) in BDL group versus sham group. Quercetin treatment significantly lowered serum levels of AST, ALT, ALP, and MPO, TNF-α, and TGF-β1 in liver tissues associated with a significant increase in serum TP and liver GPX in BDL-Q group versus BDL rats. Histological studies revealed enhancement of inflammation and a significant increase in the percentage area of collagen deposition in BDL versus sham group. These changes were attenuated in BDL-Q group compared to BDL rats. Conclusions Quercetin alleviated cholestasis induced liver injury and improved liver function possibly via attenuating liver oxidative stress, inflammation and fibrosis.

Fibroblast activation induced by common bile duct ligation in rats with obstructive jaundice

Objective To investigate the effect of common bile duct ligation on fibroblast activation in rats with obstructive jaundice. Methods Twenty-four male specific pathogen free (SPF) rats were randomly divided into sham-operated group and experimental group, with 12 rats in each group. All rats underwent common bile duct ligation. Rats The common bile duct in the experimental group was ligated with 3-0 silk thread and cut off. The rats in the two groups were sampled 2 and 7 days after operation. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of transforming growth factor-β1 (TGF-β1). Immunohistochemistry was used to detect the expression of TGF-β1 protein. The real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) was used to detect the expression of TGF-β1 gene. Western blotting was used to detect the expression of TGF-β1 protein. Results In sham-operated group, the structure of hepatic lobules was intact, and the hepatic sinuses were normal without congestion. In experimental group, the structure of hepatic lobules was disordered and the hepatic cords were dissociated. The level of serum TGF-β1 in the experimental group at 2nd day [(689.42±58.13) ng/L] and 7th day [(867.53±45.62) ng/L] was significantly higher than that in the sham-operated group [(519.92±32.41) ng/L and (536.50±41.29) ng/L, t=8.822 and 18.635, P<0.05]. The expression of TGF-β1 protein in liver tissues of experimental group at 2nd day [(6.53±1.29)%] and 7th day [(8.97±1.85)%] was significantly higher than that of sham-operated group [(1.17±0.24)% and (1.54±0.39)%, t=8.822 and 18.635, P<0.05]. The expression of TGF-β1 in liver tissues of experimental group at 2nd day [(0.89±0.14)%] and 7th day [(0.95±0.19)%] was significantly higher than that of sham-operated group [(0.52±1.32)% and (0.31±1.76)%, t=14.693 and 18.316, P<0.05]. The gray value of TGF-β1 protein expression in liver tissue of experimental group at 2nd day after operation (0.62±0.13) and 7th day after operation (0.78±0.10) was significantly higher than that of sham-operated group (0.21±0.05 and 0.23±0.06, t=10.197 and 16.337, P<0.05). Conclusion The expression of TGF-β1 in rats with obstructive jaundice induced by common bile duct ligation is significantly up-regulated, and the proliferation of biliary duct epithelial cells induces fibroblast activation. Key words: Common bile duct ligation; Obstructive jaundice; Fibroblast activation

Quercetin mitigates liver injury in a rat model of liver cholestasis

Abstract Background: cholestasis is a prevalent health problem associated with liver oxidative stress, inflammation, and fibrosis. Quercetin has been shown to afford a beneficial effect in a variety of liver diseases.This study was designed to investigate the potential protective effect of quercetin on liver cholestasis and the possible underlying mechanisms in a rat model of bile duct ligation (BDL). Methods: This study was carried out on adult male rats which were randomly divided into: Sham-operated, BDL and BDL- quercetin treated (BDL- Q) groups. Quercetin was given by gavage in a dose of 50 mg/kg/day. Results: Bile duct ligation resulted in a significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and liver levels of myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α),and transforming growth factor beta 1(TGF-β1), along with a significant decrease in serum levels of total proteins (TPs) and liver glutathione peroxidase(GPX) in BDL group versus sham-operated controls. Quercetin treatment significantly lowered serum levels of AST, ALT, ALP, and MPO, TNF-α, and TGF-β1 in liver tissues associated with a significant increase in serum TPs and liver GPX in BDL-Q group versus BDL rats. Histological studies revealed enhancement of inflammation and a significant increase in the percentage area of collagen deposition in BDL versus sham-operated group. These changes were attenuated in BDL-Q group compared to BDL rats. Conclusions: Quercetin alleviated cholestasis induced liver injury and improved liver function possibly via attenuating liver oxidative stress, inflammation and fibrosis.

Study on the association between TGF-β1 and liver fibrosis in patients with hepatic cystic echinococcosis.

The present study aimed to determine the role of the cytokine transforming growth factor-β1 (TGF-β1) in liver fibrosis among patients with hepatic cystic echinococcosis (hepatic CE). Hepatic tissue specimens and serum samples from 30 patients with hepatic CE were collected and TGF-β1 levels were compared between the two groups. The degree of liver fibrosis was assessed by Masson staining. The expression levels of cytokine TGF-β1 in liver tissue and serum were detected by immunohistochemistry and ELISA, respectively. Masson staining of liver lesion tissue in patients with hepatic CE indicated different degrees of fibrosis in the liver and the World Health Organization classification was positively correlated with the severity of liver fibrosis (P<0.05). In addition, the expression of cytokine TGF-β1 was higher in liver lesion tissue specimens compared with that in the adjacent control samples (P<0.05). At the same time, cytokine TGF-β1 in serum specimens of patients was higher than that in the healthy control group (P<0.05). In conclusion, the expression of TGF-β1 is upregulated in patients with hepatic CE, which was closely associated to liver fibrosis.

Vitamin A-coupled liposomal Rho-kinase inhibitor ameliorates liver fibrosis without systemic adverse effects.

Rho-kinase (ROCK) inhibitor could ameliorate liver fibrosis by suppressing hepatic stellate cell (HSC) activation. However, because systemic administration of ROCK inhibitor causes serious adverse effects, we developed a drug delivery system selectively delivering ROCK inhibitor to HSCs. Here, we examined whether our developed vitamin A (VA)-coupled liposomal ROCK inhibitor reduced liver fibrosis in rats without causing systemic adverse effects. LX-2 HSCs were analyzed for morphological changes and the expression of profibrotic proteins. The inhibitory effects of VA-coupled liposomal ROCK inhibitor on liver fibrosis were confirmed in a rat model of liver fibrosis induced by i.p. injection of carbon tetrachloride. The degree of liver fibrosis, biochemical changes, and survival rates were also investigated. Vitamin A-coupled liposomal ROCK inhibitor had an effect at approximately 1/100 the amount of the free ROCK inhibitor for inhibiting the activation of LX-2 cells and caused significant decreases in the expression levels of α-smooth muscle actin (SMA) and transforming growth factor (TGF)-β1. The degree of liver fibrosis was suppressed by treatment with VA-coupled liposomal ROCK inhibitor, and the expression of α-SMA and TGF-β1 in liver tissues was also significantly suppressed. In addition, serum levels of alanine aminotransferase and hyaluronic acid were significantly reduced, and there was no decline in kidney function, which has been noted as a systemic adverse effect of ROCK inhibitor. Furthermore, VA-coupled liposomal ROCK inhibitor improved survival rates in rats with liver fibrosis. Vitamin A-coupled liposomal ROCK inhibitor efficiently suppressed liver fibrosis without causing systemic adverse effects.

1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome via promoting regulatory T cell-mediated resolution of inflammation

Vitamin D3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3, significantly attenuated monosodium glutamate (MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemic-euglycemic clamp. Moreover, 1,25(OH)2D3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)2D3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied by increased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulin-targeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)2D3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.

Experimental Study &lt;i&gt;Oviductus ranae&lt;/i&gt; for the Change of α-SMA and TGF-β in Hepatic Fibrosis Rat Liver

To evaluate the control effect of Oviductus ranae on liver fibrosis in rats, and the change of TGF-β and α-SMA in liver of. To explore the mechanism of Oviductus ranae decoction on liver fibrosis. Methods Wistar female rats were randomly divided into a blank control group, model control group, colchicines group, Oviductus ranae group. Using the CCl4composite approach to make the rat modle. The course of treat-mart was 12 weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect biochemical test of liver function after eight weeks. Investigating the variation of liver histology. Meanwhile detecting protein expression of TGF-β and α-SMA and by immunehistochemical method.Result The general condition of rats in all treatment groups are worse than the blank group,but better than the model group. And the rats in the model group were all occurred in liver fibrosis,and liver fibrosis is the most serious.In a normal rat liver tissue of TGF-β and α-SMA were significantly lower in model group and each treatment group, and there were significant differences, and the TGF-β and α-SMA in expression of liver tissue in model rats of TGF-β and α-SMA the highest. Conclusion: Oviductus ranae can effectively improve liver fibrosis rats induced by CC14liver function.Oviductus ranae can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CCl4in. This may be one of the mechanisms of Oviductus ranae in prevention and treatment of liver fibrosis. Even though both increased expression of TGF-β and α-SMA expression, is able to determine TGF-β and α-SMA for the intervention of liver TGF-β signal transduction pathway in liver fibrosis.

Preventive effect of exogenous hydrogen sulfide on hepatic fibrosis in rats

To determine the effect of exogenous hydrogen sulfide on experimental hepatic fibrosis in rats and its mechanism. Wistar male rats were randomly divided into three groups: a normal control group (n=8), a model group (n=8), and a hydrogen sulfide prevention group (n=8). The rat model of hepatic fibrosis was reduced by intraperitoneal injection of carbon tetrachloride (CCl4). The prevention group, in addition to intraperitoneal injection of 40% CCl4, was intraperitoneally administered H2S once a day until 8th week. After the experiment, the liver function and liver fibrosis were assayed. Liver tissue samples were used for histopathological changes. The expression of TGF-β1 in liver tissue was detected by RT-PCR and Western blot. Compared with the model group, the levels of ALT, AST, HA, LN, and PC III in the sulfide group were significantly reduced (P<0.01 or P<0.05), ALB content was increased (P<0.05) in the serum, TGF-β1 expression was obviously reduced, and the degree of liver fibrosis was improved (P<0.05). Exogenous hydrogen sulfide can effectively inhibit the development of hepatic fibrosis, reduce the expression of TGF-β1, and decrease the the sediment of extracellular matrix in the liver tissues.

Effects and mechanism of sophocarpine in rats with alcoholic liver disease

Objective To investigate the efficacy of sophocarpine in rats with alcoholic liver disease and its effects on the expression of tumor necrosis factor (TNF)-α,interleukin (IL)-6 and transforming growth factor (TGF)-β1.Methods A total of 48 male Sprague-Dawley adult rats were evenly divided into healthy control group,model group,prevention group and treatment group.The rats in the healthy control group were gavaged with 0.9％NaCl every day for 12 weeks.The rats in the model group,prevention group and treatment group were gavaged with alcohol for 12 weeks to establish the model.The prevention group was injected with 20 mg · kg1 · d1 sophocarpine for 12 weeks.Since the fifth week,the treatment group was continuously injected with 20 mg · kg1 · d-1 sophocarpine for eight weeks.The histological changes were evaluated.The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase ( AST ), alkaline phosphatase (AKP),triglyceride (TG) and total cholesterol (TC) were examined.And the expression of TNF-α,IL-6 and TGF-β1 in liver tissue at mRNA and protein level were detected with immunohistochemistry and real-time polymerase chain reaction (PCR) assay.Comparison among groups was perform with single factor analysis of variance,pairwise comparisons with least significant difference method (LSD method),ranked data with Kruskal-Wallis H-test and multiple pairwise comparison with Nemenyi test.Results Compared with model group,hepatic steatosis and inflammatory cell infiltration were significantly improved in the treatment group and prevention group.The levels of ALT (41.40 U/L± 10.53 U/L and 40.75 U/L±6.94 U/L vs 58.37 U/I±5.35 U/L),AST(121.60 U/L±16.24 U/L and 109.50 U/L±9.23 U/L vs 156.63 U/L±32.47 U/L),AKP(114.88 U/L±40.37 U/L and 112.60 U/L±44.34 U/L vs 161.75 U/L±28.95 U/L),TG (4.19 mmol/L±0.99 mmol/L and 2.69 mmol/L± 1.35 mmol/L vs 4.50 mmol/L±0.99 mmol/L) and TC (1.48 mmol/L±0.28 mmol/L and 1.43 mmol/L±0.19 mmol/L vs 1.67 mmol/L±0.20 mmol/L) significantly decreased and the difference was statistically significant ( all P＜0.05).The expression of TNF-α,IL-6 and TGF-β1 at mRNA and protein level in liver tissue of model group were significantly higher than those of healthy control group,prevention group and treatment group.After treated with sophocarpine,the expression of TNF-α(mRNA:1.36 ± 0.08,1.16 ± 0.05 ; protein:3.38 ％ ± 0.82 ％,1.74 ％ ± 0.65 ％ ),IL-6 (mRNA:1.51 ± 0.05,1.39 ± 0.02; protein:5.89％ ± 0.96％,4.26％ ± 0.53％) and TGF-β1 (mRNA:1.39±0.04,1.37±0.02; protein:4.27％ ±0.97％,2.11％ ±0.83％) of treatment group and prevention group at mRNA and protein level significantly lower than those of model group (mRNA:1.81±0.16,1.95 ±0.13,1.84±0.22; protein:5.82％ ± 1.21％,7.63％ ±1.03％,5.33％± 1.12％) and the difference was statistically significant (all P＜0.01).Conclusion Sophocarpine significantly alleviates alcohol induced liver injury in rats,improves liver steatosis and inflammatory reaction degree,which may be related with the downregulation of TNF-α,TGF-β1 and IL-6 expression in liver tissue of ALD rats. Key words: Liver diseases, alcoholic; Alkaloids; Tumor necrosis factor-alpha; Interleukin-6; Transforming growth factor betal

TNF-α, HGF and TGF-β1 are Involved in Liver Regeneration Following Partial Hepatectomy Using Portal Vein Arterializations

TNF-α, HGF and TGF-β1 are Involved in Liver Regeneration Following Partial Hepatectomy Using Portal Vein ArterializationsExperiments on liver regeneration after partial hepatectomy have shown that TNF-α, HGF and TGF-β1 and other cytokines play important roles in the different stages of liver regeneration, however, the effect of portal vein arterialization (PVA) on the expressions of these cytokines during liver regeneration is not clear. Sprague Dawley rats were randomly divided into the PVA group and control groups, and blood was collected for the detection of ALT using an automatic biochemical analyzer. The expressions of TNF-α, HGF and TGF-β1 in liver tissues were detected by quantitative RT-PCR. The ALT levels in both groups in the early period after surgery were significantly higher than those before operation, and gradually returned to normal at 7 days after surgery. At 12 h and 24 h after operation, the TNF-α expression in the PVA group was significantly higher than that in the control group (P&lt;0.05), but no significant difference at 7 days after surgery was observed between the two groups. At 12 h, the HGF expression in the PVA group was similar to that in the control group, but significantly higher than in the control group at 24 h (P&lt;0.05). At 24 h, the TGF-β1 expression in the PVA group was significantly lower than that in the control group (P &lt;0.05), but no significant difference was found at 48 h after surgery between the two groups. The promotive effects on the portal vein arterialization at the early stage of liver regeneration were associated with the changes in the expressions of TNF-α, HGF and TGF-β1.

Level of serum and liver tissue TGF-beta1 in patients with liver fibrosis due to chronic hepatitis B

To detect the level of serum and liver tissue TGF-beta1 in patients with chronic hepatitis B, to study their relation to liver fibrosis and gain the evidence for diagnosis of liver fibrosis. The liver fibrosis grades (S0-S4) of 131 cases with chronic HBV infection were diagnosed after liver biopsy. Serum TGF-beta1 was detected by enzyme-linked immunosorbent assay, and the semiquantitative analysis was applied after detecting the expression of TGF-beta1 in liver tissue with immunohistochemistry. Their relations to liver fibrosis were analyzed. Serum and tissue level of TGF-beta1 increased significantly with the development of fibrosis, and the same result was obtained between themselves (P < 0.01). There was very significant difference for serum level of TGF-beta1 among the groups with different fibrosis grades (P < 0.01). Serum levels of TGF-beta1 were decreased significantly comparing the Group S0 or S1 to S4 (P < 0.005). There were significant difference for serum level of TGF-beta1 among S0 and the others (P < 0.005). And there was significant difference between S1 and S3 (P < 0.005). The expression level of TGF-beta1 in liver tissue has no significant difference between group S3 and S4 (P > 0.05). However, the differences were significantly among the other comparisons (P < 0.01). There is close relation between the level of TGF-beta1 and the different liver fibrosis grades due to chronic hepatitis B. The serum level of TGF-beta1 is a potential noninvasive maker for diagnosis of liver fibrosis.