Effects and mechanism of adenovirus-mediated phosphatase and tension homologue deleted on chromosome ten gene on collagen deposition in rat liver fibrosis

Xie, Shurui; An, Jun-Yan; Zheng, Libo; Huo, Xiaoxia; Guo, Jun; Shih, David Q.; Zhang, Xiaolan

doi:10.3748/wjg.v23.i32.5904

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…AKT is a pro-cell survival protein that is well documented for its role in HSC proliferation and migration [13,46]. A recent report suggests that PTEN overexpression by adenovirus in the CCl 4 -induced rat liver fibrosis model reduced serum ALT and AST while decreasing collagen deposition in the liver [47]. Here, we report that adiponectin can prevent the loss of PTEN during CCl 4 -induced liver fibrosis and in activated HSCs.…”

Section: Discussionsupporting

confidence: 52%

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Kumar¹,

Raeman²,

Chopyk³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Adiponectin inhibits hepatic stellate cell (HSC) activation and subsequent development of liver fibrosis via multiple mechanisms. Phosphatase and tensin homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation, but its regulation by adiponectin is not fully understood. Here, we investigated the effect of adiponectin on PTEN in LX-2 cells, a human cell line and examined the underlying molecular mechanisms involved in adiponectin-mediated upregulation of PTEN activity during fibrosis. PTEN expression was found to be significantly reduced in the livers of mice treated with CCl4, whereas its expression was rescued by adiponectin treatment. The DNA methylation proteins DNMT1, DNMT3A, and DNMT3B are all highly expressed in activated primary HSCs compared to quiescent HSCs, and thus represent additional regulatory targets during liver fibrogenesis. Expression of DNMT proteins was significantly induced in the presence of fibrotic stimuli; however, only DNMT3B expression was reduced in the presence of adiponectin. Adiponectin-induced suppression of DNMT3B was found to be mediated by enhanced miR-29b expression. Furthermore, PTEN expression was significantly increased by overexpression of miR-29b, whereas its expression was markedly reduced by a miR-29b inhibitor in LX-2 cells. These findings suggest that adiponectin-induced upregulation of miR-29b can suppress DNMT3B transcription in LX-2 cells, thus resulting in reduced methylation of PTEN CpG islands and ultimately suppressing the PI3K/AKT pathway. Together, these data suggest a possible new explanation for the inhibitory effect of adiponectin on HSC activation and liver fibrogenesis.

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Section: Discussionsupporting

confidence: 52%

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Kumar¹,

Raeman²,

Chopyk³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“… 29 The degree of collagen deposition and fibrosis is critically regulated by the balance between MMPs and TIMPs. 30 In this current study, pro-MMP-9 levels were decreased and TIMP-1 levels were increased in the livers of HFD-fed NAFLD rats. These results were consistent with the report that TIMP-1 expression was inhibited in the CCl 4 -induced rat hepatic fibrosis model.…”

Section: Discussionsupporting

confidence: 48%

“…These results were consistent with the report that TIMP-1 expression was inhibited in the CCl 4 -induced rat hepatic fibrosis model. 30 However, higher pro-MMP-9 levels were found in the arnebin-1 treatment groups than in the NAFLD group. Moreover, HFD-induced TIMP-1 expression was significantly downregulated after arnebin-1 treatment.…”

Section: Discussionmentioning

confidence: 92%

Protective role of arnebin-1 in rats with nonalcoholic fatty liver disease

Yang

Yao

et al. 2019

J Int Med Res

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Objective To examine the effects of arnebin-1 on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). Methods Male Sprague–Dawley rats were fed an HFD for 10 weeks and then treated with arnebin-1 at a dose of 5, 10 or 20 mg/kg/day by gavage for a further 12 weeks of a 22-week HFD. Peripheral blood and liver tissues were collected for biochemical and histopathological examination. The mechanisms of arnebin-1 on liver fibrosis and insulin resistance (IR) were determined by Western blotting and real-time quantitative polymerase chain reaction. Results Arnebin-1 treatment attenuated the increase of total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase in serum and lipid accumulation in the livers of HFD-fed rats. Furthermore, arnebin-1 abrogated HFD-induced liver fibrosis and the increase of fibrotic biomarkers. The HFD-induced decrease of hepatic proliferator-activated receptor γ and pro-matrix-metalloproteinase (MMP)-9 levels and the increase of tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were reversed after arnebin-1. Arnebin-1 attenuated IR through activating the insulin receptor substrate-1/Akt/mTOR signalling pathway. Conclusion This study demonstrated that arnebin-1 ameliorates NAFLD, in part, by attenuating hepatic fibrosis and IR, suggesting that arnebin-1 may be a therapeutic agent for NAFLD treatment.

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“…As collagen deposition is a marker for liver fibrosis ( 25 ), liver fibrosis in murine liver sections was assessed using sirius red staining in the present study ( Fig. 6D ).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic effects of mesenchymal stem cells combined with short hairpin RNA on liver injury induced by hepatitis B virus infection

Liu

Wang

et al. 2017

Mol Med Report

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The clinical symptoms of chronic hepatitis B virus (HBV) infection include severe liver damage, which is associated with the elimination of the HBV-infected cells by the immune system. It has been suggested that suppression of HBV replication is not sufficient for patients with hepatitis B and the damaged liver function requires restoration. In the present study, mesenchymal stem cells (MSCs) were combined with short hairpin (sh)RNA to treat liver injury and suppress HBV replication in a mouse model. Lx-shRNA157-1694 (an shRNA expression plasmid containing two shRNA expression cassettes) and mouse immortal (mi)MSCs stably expressing shRNA (miMSC-shRNA) were constructed and their suppressive effects on HBV expression were investigated using reverse transcription-polymerase chain reaction (RT-PCR), ELISA and immunofluorescence. Hepatogenic differentiation of miMSC-shRNA was induced in vitro and confirmed by morphology, reverse transcription-semi-quantitative and -quantitative PCR, urea production and Periodic acid-Schiff staining analyses. miMSCs and the shRNA expression plasmid alone or combined with miMSCs stably expressing shRNA were injected into mice. The former therapeutic regimen successfully suppressed HBV expression in sera and liver tissue, whereas the latter only suppressed HBV expression in liver tissue. Analyses of serum alanine aminotransferase levels, aspartate aminotransferase levels, liver weight/body weight ratio percentage and sirius red staining demonstrated marked amelioration of liver injury in mice treated with both therapeutic regimens. The results of the present study suggest that miMSCs combined with shRNA treatment may alleviate liver injury and suppress HBV expression, thus providing a novel potential therapeutic strategy for the treatment of liver injury induced by HBV infection.

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Effects and mechanism of adenovirus-mediated phosphatase and tension homologue deleted on chromosome ten gene on collagen deposition in rat liver fibrosis

Cited by 10 publications

References 26 publications

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Protective role of arnebin-1 in rats with nonalcoholic fatty liver disease

Therapeutic effects of mesenchymal stem cells combined with short hairpin RNA on liver injury induced by hepatitis B virus infection

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