Treatment with human metalloproteinase-8 gene delivery ameliorates experimental rat liver cirrhosis

Siller-López, Fernando; Sandoval, Ana; Salgado, Silvia; Salazar, Andrea; Bueno-Topete, Miriam Ruth; Garcı́a, Jesús; Vera, José; Villafuerte-Gálvez, Javier; Hernández, Ivan; Ramos, Martha H.; Aguilar-Córdova, Estuardo; Armendáriz‐Borunda, Juan

doi:10.1053/j.gastro.2003.12.045

Cited by 158 publications

(122 citation statements)

References 38 publications

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“…24,25 In addition, a single gene delivery of MMP-8 with adenoviral vectors led to amelioration of fibrosis in both BDL and CCl4-induced fibrosis models. 26 We discovered in the current study that DPIM not only suppressed the expression of TIMP-1 (Figures 5a and b), but also enhanced the expression of collagenase MMP-8 ( Figure 5c). We also detected the enhanced expression (Figures 5d and e) and activity ( Figure 6) of MMP-2 and MMP-9 (gelatinase) by DPIM.…”

Section: Discussionsupporting

confidence: 57%

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

Ding

Kng

Yang

et al. 2011

Laboratory Investigation

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Hepatic fibrosis is the result of chronic liver injuries underlined by diverse etiologies. The massive accumulation of extracellular matrix (ECM) proteins during fibrogenesis leads to structural distortion and functional disruption of the liver. There is currently no effective standard treatment for liver fibrosis. We previously identified a class of imidazolium salts (IMSs) with anti-fibrotic properties in a cell-based screen. In this report, we investigated the anti-fibrotic efficacy and mechanisms of a small IMS, 1,3-diisopropylimidazolium tetrafluoroborate (DPIM), in a hepatic fibrosis model induced by bile duct ligation (BDL) in mice. The orally available DPIM was administered to BDL mice via drinking water at three concentrations (0.5, 0.75, and 1 g/l) for 4 weeks. We observed a significant reduction in inflammation and collagen deposition in the liver, which could be mediated by a reduction in the expression of monocyte chemoattractant protein-1 (MCP-1) and by an enhancement in the matrix metalloproteinase-mediated ECM remodeling. The current findings highlight the importance for simultaneously targeting multiple pathways to more effectively attenuate and resolve liver fibrosis and warrant further studies on this compound in additional models of hepatic fibrosis.

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Section: Discussionsupporting

confidence: 57%

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

Ding

Kng

Yang

et al. 2011

Laboratory Investigation

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“…17,25 Adenoviral gene delivery of human MMP-1 or MMP-8 in a rat liver with cirrhosis induced by thioacetamide, CCl 4 , or BDL resulted in the regression of fibrosis. In all cases, adenovirus delivery of collagenase to the liver was performed during the spontaneous recovery phase, when the inducing agent was removed.…”

Section: Discussionmentioning

confidence: 99%

Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis

et al. 2006

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“…31,32 By contrast, hepatic overexpression of MMPs ameliorates experimental fibrosis. 33 Augmentation of spontaneous resolution of liver fibrosis via stimulation of HSC apoptosis is associated with a 40% diminution of hepatic TIMP-1 and a 30% elevation of hepatic MMP activity. 34 Hence, the 78% difference between junD Ϫ/Ϫ and wt mice in level of hepatic TIMP-1 would signifi- cantly attenuate collagenolytic activity and result in reduced matrix deposition.…”

Section: Discussionmentioning

confidence: 99%

JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation

et al. 2006

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A ctivated (or myofibroblastic) hepatic stellate cells (HSCs) are cellular mediators of liver fibrosis through their secretion of interstitial collagens and tissue inhibitor of metalloproteinase-1 (TIMP-1), 1,2 which is a broad specific inhibitor of the matrix metalloproteinases (MMPs) and prevents MMP-catalyzed degradation of interstitial collagens in order to promote collagen deposition. A second fibrogenic role identified for TIMP-1 is as a suppressor of HSC apoptosis. 3 TIMP-1 gene transcription is induced during culture activation of isolated HSCs and is under the control of regulatory elements in the TIMP-1 promoter including activator protein-1 (AP-1) and RUNX binding sites. [4][5][6][7]

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Treatment with human metalloproteinase-8 gene delivery ameliorates experimental rat liver cirrhosis

Cited by 158 publications

References 38 publications

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis

JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation

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