Hepatic Stellate Cell Activation and Hepatic Fibrosis Induced by Ischemia/Reperfusion Injury

Cheng, Feng; Li, Y.; Li, Feng; Li, S.

doi:10.1016/j.transproceed.2008.06.052

Cited by 29 publications

(25 citation statements)

References 19 publications

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“…In the present study, all three types of myofibroblasts were seen, denoting their phenotypical heterogeneity. Our results showed that quiescent HSCs in control liver express vimentin and desmin but not ␣-SMA, while activated HSCs in the fibrotic lesion express vimentin, desmin and ␣-SMA, supporting that ␣-SMA is a reliable marker of HSC activation and transformation to myofibroblasts during liver fibrosis (Cheng et al, 2008).…”

Section: Properties Of Gfap-positive Myofibroblasts In Liver Cirrhosissupporting

confidence: 67%

Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)

Tennakoon

Izawa

Wijesundera

et al. 2015

Experimental and Toxicologic Pathology

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Section: Properties Of Gfap-positive Myofibroblasts In Liver Cirrhosissupporting

confidence: 67%

Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)

Tennakoon

Izawa

Wijesundera

et al. 2015

Experimental and Toxicologic Pathology

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“…Insufficient immunosuppression can be a risk factor of development of graft fibrosis and chronic rejection (38); however, this explanation seems unlikely because the fibrosis was already noted after LTx when both the cellular and humoral alloimmune responses were abolished by ASKP1240 administration, as shown by several assays. Rather, this rapid peri-portal fibrotic change seems to be a hallmark of IRI, which has been shown previously to play a major role in graft fibrosis in the liver (39) and other organs (40). In fact, the cynomolgus monkey liver was very susceptible to ischemia: in our preliminary study, most of recipient monkeys died within 24 hours after LTx because the veno-veno bypass was not applicable in these small monkeys.…”

Section: Discussionmentioning

confidence: 54%

Long-Term Hepatic Allograft Acceptance Based on CD40 Blockade by ASKP1240 in Nonhuman Primates

Oura

Yamashita

Suzuki

et al. 2012

American Journal of Transplantation

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Blockade of the CD40-CD154 costimulatory signal is an attractive strategy for immunosuppression and tolerance induction in organ transplantation. Treatment with anti-CD154 monoclonal antibodies (mAbs) results in potent immunosuppression in nonhuman primates (NHPs). Despite plans for future clinical use, further development of these treatments was halted by complications. As an alternative approach, we have been focusing on the inhibition of the counter receptor, CD40 and have shown that a novel human anti-CD40 mAb, ASKP1240, markedly prolongs renal allograft survival in NHPs, although allografts eventually underwent chronic allograft nephropathy. On the basis of our previous findings that a CD40-CD154 costimulation blockade induces tolerance to hepatic, but not cardiac, allografts in rodents, we tested here our hypothesis that a blockade of CD40 by ASKP1240 allows acceptance of hepatic allografts in NHPs. A 2-week ASKP1240 induction treatment prolonged liver allograft survival in NHPs; however, the graft function deteriorated due to chronic rejection. In contrast, a 6-month ASKP1240 maintenance monotherapy efficiently suppressed both cellular and humoral alloimmune responses and prevented rejection on the hepatic allograft. No serious side effects, including thromboembolic complications, were noted in the ASKP1240-treated monkeys. We conclude that CD40 blockade by ASKP1240 would be a desirable immunosuppressant for clinical liver transplantation.

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“…Our study showed that chronic exposure to CCl 4 activated the Hh signaling pathway, which was manifested as the elevated mRNA and protein levels of Hh ligand Shh and transcription factor Gli1. Meanwhile, during the course of CCl 4 -induced liver fibrogenesis, the increases of hepatic collagen content and EMT markers expression in liver tissues of fibrotic model rats were paralleled by the elevation of Hh pathway activity, which also proved that the dysregulation of Hh signaling pathway plays a pivotal role in modulating liver injury and initiation of EMT that accelerates the induction of fibrosis [7, 27]. After DWYG treatment, the expressions of Hh ligand Shh, membrane-spanning receptor Smo and its co-receptor Ptc, and transcription factor Gli1 in CCl 4 -induced fibrotic liver tissue were dramatically repressed, suggesting that the activity of Hh signaling pathway was inhibited.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of early liver fibrosis by herbal compound “Diwu Yanggan” through modulating the balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition

Shen

Cheng

et al. 2014

BMC Complement Altern Med

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BackgroundDiwu Yanggan (DWYG) is a Chinese compound herbal preparation which consists of five Chinese herbs. This study investigates the preventative effects of DWYG on liver fibrosis induced by carbon tetrachloride (CCl4) and explores its possible mechanisms of action.MethodsLiver fibrosis was induced in male Wistar rats by injecting a 50% CCl4/soybean oil solution subcutaneously twice a week for six weeks. After six weeks of treatment, serum aspartate transaminase (AST) and alanine transaminase (ALT) assay, liver tissue histological assessment and hepatic hydroxyproline assay were respectively carried out to examine the effects of DWYG on liver function and fibrosis degree. The impacts of DWYG on the expression levels of epithelial marker E-cadherin, mesenchymal marker Vimentin, transforming growth factor β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) were further examined by quantitative real-time RT-PCR and Western blot analysis. In addition, the differences of Hedgehog (Hh) signaling pathway activity between DWYG-treated and DWYG-untreated fibrotic liver tissues were also evaluated by quantitative real-time RT-PCR and Western blot analysis.ResultsUpon DWYG treatment, the serum levels of ALT and AST, hepatic hydroxyproline content and the degree of fibrosis in CCl4-induced fibrotic model rats were dramatically declined. In accompany with the alleviation of the degree of fibrosis, DWYG treatment provoked the reversal of epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) in the fibrotic liver tissues, which was characterized with the up-regulation expression of E-cadherin and down-regulation expression of Vimentin. Furthermore, we observed that the expression level of TGF-β1 was reduced whereas the expression level of BMP-7 was enhanced in liver tissues of DWYG-treated rats, therefore the expression ratio of TGF-β1/BMP-7 was dramatically decreased compared to CCl4-induced fibrosis model rats. In addition, quantitative real-time RT-PCR and Western blot analysis demonstrated that after DWYG treatment the expressions of Hh ligand Shh, receptor Smo and Ptc, and transcription factor Gli1 in CCl4-induced fibrotic liver tissues were dramatically repressed.ConclusionsDWYG demonstrates therapeutic potential to prevent liver fibrosis by modulating the balance between EMT and MET through reducing the expression ratio of TGF-β1/BMP-7 and inhibiting the excessive activation of Hh signaling pathway.

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Hepatic Stellate Cell Activation and Hepatic Fibrosis Induced by Ischemia/Reperfusion Injury

Cited by 29 publications

References 19 publications

Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)

Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)

Long-Term Hepatic Allograft Acceptance Based on CD40 Blockade by ASKP1240 in Nonhuman Primates

Attenuation of early liver fibrosis by herbal compound “Diwu Yanggan” through modulating the balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition

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