Interferon gamma peptidomimetic targeted to hepatic stellate cells ameliorates acute and chronic liver fibrosis in vivo

Bansal, Ruchi; Prakash, Jai; Ruiter, M.; Poelstra, Klaas

doi:10.1016/j.jconrel.2014.01.022

Cited by 43 publications

(36 citation statements)

References 42 publications

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“…Unfortunately, a multicenter, randomized, placebo-controlled trial of subcutaneously injected recombinant IFN-c found no improvement in the survival of patients with IPF [209], substantially lowering enthusiasm for further exploration of antifibrotic applications of this cytokine, especially in light of its expected side effects on immune regulation. Ongoing work focuses on developing IFN-c derivatives, such as peptidomimetics that retain antifibrotic activity but lack off-target effects of native IFN-c and may thus become a viable antifibrotic therapy in the future [210].…”

Section: Ifn-cmentioning

confidence: 99%

The cytokines of pulmonary fibrosis: Much learned, much more to learn

et al. 2015

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Section: Ifn-cmentioning

confidence: 99%

The cytokines of pulmonary fibrosis: Much learned, much more to learn

et al. 2015

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Section: Discussionmentioning

confidence: 99%

“…More recently, the IFN-␥ mimetic has been developed for the treatment of hepatic fibrosis (28,29). IFN-␥ has been shown to be a potent antifibrotic, but its use in the treatment of hepatic fibrosis is limited by matters, such as undesirable side effects (28,29). The undesirable side effects of IFNs have been shown to be due to extracellular receptor interaction (30), so in the absence of such binding by the IFN-␥ mimetic, it functioned when targeted to hepatic tissue as a potent antifibrotic without the undesirable side effects.…”

Section: Discussionmentioning

confidence: 99%

Type I Interferon Mimetics Bypass Vaccinia Virus Decoy Receptor Virulence Factor for Protection of Mice against Lethal Infection

Ahmed

Johnson

2014

Clin. Vaccine Immunol.

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“…PEGylation significantly improved the pharmacokinetics, liver uptake, and anti-fibrotic effects of IFNγ (Bansal et al 2011). The novel chimeric molecule contains the IFNγ signaling peptide (mimγ) that has the agonistic activity of IFNγ is coupled to PDGF-βR-binding peptide (BiPPB) by a PEG linker can inhibit early liver fibrosis in CCl4-treated mice (Bansal et al 2014). The "hepato-protectants" such as HGF (hepatocyte growth factor) and insulin growth factor (IGF) also have potent anti-apoptotic and mitogenic effects on hepatocytes during liver injury and essential roles in liver regeneration.…”

Section: Improvement Of Liver Function and Enhanced Liver Regenerationmentioning

confidence: 99%

Strategies to prevent and reverse liver fibrosis in humans and laboratory animals

Chen

Wang

2015

Arch Toxicol

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Liver fibrosis results from chronic damage to the liver in conjunction with various pathways and is mediated by a complex microenvironment. Based on clinical observations, it is now evident that fibrosis is a dynamic, bidirectional process with an inherent capacity for recovery and remodeling. The major mechanisms involved in liver fibrosis include the repetitive injury of hepatocytes, the activation of the inflammatory response after injury stimulation, and the activation and proliferation of hepatic stellate cells (HSCs), which represents the major extracellular matrix (ECM)-producing cells, stimulated by hepatocyte injury and inflammation. The microenvironment in the liver is synergistically regulated abnormal ECM deposition, scar formation, angiogenesis, and fibrogenesis. Moreover, recent studies have clarified novel mechanism in fibrosis such as epigenetic regulation of HSCs, the leptin and PPARγ pathways, the coagulation system, and even autophagy. Uncovering the mechanisms of liver fibrogenesis provides a basis to develop potential therapies to reverse and treat the fibrotic response, thereby improving the outcomes of patients with chronic liver disease. Although both scientific and clinical challenges remain, emerging studies attempt to reveal the ideal anti-fibrotic drug that could be easily delivered to the liver with high specificity and low toxicity. This review highlights the mechanisms, including novel pathways underlying fibrogenesis that may be translated into preventive and treatment strategies, reviews both current and novel agents that target specific pathways or multiple targets, and discusses novel drug delivery systems such as nanotechnology that can be applied in the treatment of liver fibrosis. In addition, we also discuss some current treatment strategies that are being applied in animal models and in clinical trials.

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Interferon gamma peptidomimetic targeted to hepatic stellate cells ameliorates acute and chronic liver fibrosis in vivo

Cited by 43 publications

References 42 publications

The cytokines of pulmonary fibrosis: Much learned, much more to learn

The cytokines of pulmonary fibrosis: Much learned, much more to learn

Type I Interferon Mimetics Bypass Vaccinia Virus Decoy Receptor Virulence Factor for Protection of Mice against Lethal Infection

Strategies to prevent and reverse liver fibrosis in humans and laboratory animals

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