Expression of Discoidin Domain Receptors (DDR2) in Alcoholic Liver Fibrosis in Rats

Xi-hong, Zhang; Yan, Mingxia; Liu, Li; Wu, Tiejun; Ma, Lei; Wang, Lexin

doi:10.1016/j.arcmed.2010.10.010

Cited by 22 publications

(10 citation statements)

References 12 publications

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“…Rats received alcohol infusions via gavage to induce liver fibrosis, similar to the procedure used by Zhang et al (11). Alcohol was administered at 5.0 g/kg/day from 1-4 weeks, 7.0 g/kg/day from 5-8 weeks, 9.0 g/kg/day from 9-12 weeks and 9.5 g/kg/day from 13-24 weeks.…”

Section: Induction Of Ahfmentioning

confidence: 99%

Cilostazol protects rats against alcohol‑induced hepatic fibrosis via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway

2019

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Alcohol abuse and chronic alcohol consumption are major causes of alcoholic liver disease worldwide, particularly alcohol-induced hepatic fibrosis (AHF). Liver fibrosis is an important public health concern because of its high morbidity and mortality. The present study examined the mechanisms and effects of the phosphodiesterase III inhibitor cilostazol on AHF. Rats received alcohol infusions via gavage to induce liver fibrosis and were treated with colchicine (positive control) or cilostazol. The serum alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities and the albumin/globulin (A/G), enzymes and hyaluronic acid (HA), type III precollagen (PC III), laminin (LA), and type IV collagen (IV-C) levels were measured using commercially available kits. α-smooth muscle actin (α-SMA), collagen I and III, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), adenosine 3',5'-cyclic monophosphate (cAMP) and exchange protein directly activated by cAMP (Epac) 1/2 expression in liver tissue were measured using western blotting. The results demonstrated that cilostazol significantly increased the serum ADH and ALDH activities and decreased the liver hydroxyproline levels. Cilostazol increased the serum A/G ratio and inhibited the total serum protein, enzymes, HA, PCIII, LA and IV-C levels. Western blotting revealed that cilostazol effectively decreased liver α-SMA, collagen I and III, TGF-β1 and CTGF expression. Cilostazol significantly increased the cAMP and Epac1 levels in hepatic tissue. The present study suggests that cilostazol protects rats against AHF via suppression of TGF-β1/CTGF activation and the cAMP/Epac1 pathway.

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Section: Induction Of Ahfmentioning

confidence: 99%

Cilostazol protects rats against alcohol‑induced hepatic fibrosis via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway

2019

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“…Animals in Groups II-VI were given intragastric alcohol infusion to induce liver fibrosis. The concentration and amount of alcohol was increased gradually according to the previous study 18) : 5.0 g/kg/d from 1 to 4 weeks; 7.0 g/kg/d from 5 to 8 weeks; 9.0 g/kg/d from 9 to 12 weeks; and 9.5 g/kg/d from 13 to 24 weeks. Group II served as alcohol-induced liver fibrosis model.…”

Section: Methodsmentioning

confidence: 99%

Combination Therapy with Taurine, Epigallocatechin Gallate and Genistein for Protection against Hepatic Fibrosis Induced by Alcohol in Rats

Zhuo

Liao

et al. 2012

Biological & Pharmaceutical Bulletin

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This study was to investigate the possibility of enhancing the anti-fibrotic effect by using a combination therapy with taurine, epigallocatechin gallate and genistein in a rat liver fibrosis model induced by alcohol, and to explore its underlying mechanism. Hepatic fibrosis was induced by intragastric administration with various amount of alcohol (5.0-9.5 g/kg) within 24 weeks in rats. The model group received alcohol only, and treatment groups received the corresponding drugs plus alcohol respectively, while the normal control group received an equal volume of saline. The antifibrotic effects of combination therapy were assessed directly by hepatic histology, and indirectly by measurement of serum biochemical markers, the fibrosis markers and related key cytokines/proteins. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyltransferase, interleukin-6 and tumor necrosis factor-α. Moreover, combination therapy could effectively suppress the serum levels of fibrosis markers and hepatic hydroxyproline content, inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that combination therapy was able to markedly reduce lipid peroxidation and recruit the anti-oxidative defense system, and inhibit the expression of B-cell lymphoma 2, α-smooth muscle actin, transforming growth factor β 1 and small mothers against decapentaplegic homolog 3 proteins. Our results showed that combination therapy is effective in attenuating hepatic injury and fibrosis in the alcohol-induced rat model. The improved efficacy of the combination therapy with its good safety profile could represent a new protective approach for liver fibrosis.

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“…So we supposed that DDR2 may play a different role in certain stages of chronic liver disease. Because the ingestion course of alcoholic liver fibrosis model is from 12 to 20 weeks [23], [43], we tried to treat rats with alcohol for 10 weeks. As a result, acetaldehyde or alcohol induced the expression of DDR2 in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…DDR2 is expressed in some tumor cells and some fibrotic diseases of the heart, lung, kidney, cartilage, skin and liver [19], [20], [21]. DDR2 expression induced in liver fibrosis models was detected in activated HSCs but not hepatocytes or Kupffer cells [22], [23], [24]. DDR2 is characterized by 3 distinct regions: an extracellular domain for collagen binding, a transmembrane region and an intracellular kinase domain [25].…”

Section: Introductionmentioning

confidence: 99%

RNA Interference against Discoidin Domain Receptor 2 Ameliorates Alcoholic Liver Disease in Rats

et al. 2013

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Discoidin domain receptor 2 (DDR2) is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.

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Expression of Discoidin Domain Receptors (DDR2) in Alcoholic Liver Fibrosis in Rats

Cited by 22 publications

References 12 publications

Cilostazol protects rats against alcohol‑induced hepatic fibrosis via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway

Cilostazol protects rats against alcohol‑induced hepatic fibrosis via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway

Combination Therapy with Taurine, Epigallocatechin Gallate and Genistein for Protection against Hepatic Fibrosis Induced by Alcohol in Rats

RNA Interference against Discoidin Domain Receptor 2 Ameliorates Alcoholic Liver Disease in Rats

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