Anti-fibrogenic strategies and the regression of fibrosis

Kisseleva, Tatiana; Brenner, David A.

doi:10.1016/j.bpg.2011.02.011

Cited by 147 publications

(115 citation statements)

References 115 publications

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“…Pivotal studies have demonstrated that liver fibrosis is not always an irreversible condition provided that underlying etiological agents are removed, as has been the case with secondary biliary fibrosis, Hepatitis C, Hepatitis B, steatohepatitis, and autoimmune hepatitis [192].…”

Section: Ppars Stimulation Strategies Therapymentioning

confidence: 99%

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Zardi¹,

Navarini²,

Sambataro³

et al. 2013

CMC

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Abstr act: Complex molecular and cellular mechanisms are involved in the pathway of liver fibrosis. Activation and transformation of hepatic stellate cells (HSCs) are considered the two main reasons for the cause and development of liver fibrosis. The peroxisome proliferator-activated receptors (PPARs) belonging to the family of ligand-activated transcription factors play a key role in liver homeostasis, regulating adipogenesis and inhibiting fibrogenesis in HSCs. Normal transcriptional function of PPARs contributes to maintain HSCs in quiescent phase. A reduced expression of PPARs in HSCs greatly induces a progression of liver fibrosis and an increased production of collagen. Here, we discuss role and function of PPARs and we take into consideration molecular factors able to reduce PPARs activity in HSCs. Finally, although further validations are needed, we illustrate novel strategies available from in vitro and animal studies on how some PPARs-agonists have been proved effective as antifibrotic substances in liver disease.

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Section: Ppars Stimulation Strategies Therapymentioning

confidence: 99%

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Zardi¹,

Navarini²,

Sambataro³

et al. 2013

CMC

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“…However, the in vivo inhibition of endogenous TIMP-1 expression remained unclear. Recombinant adenovirus is highly efficient for both in vitro and in vivo transfection, for a wide range of infected cells, it can infect quiescent and mitotic cells, and it does not integrate into the host cell genome; thus, the adenovirus has wide application potential in gene engineering and gene therapy (Hammann et al, 2007;Kisseleva and Brennern, 2011). In this experiment, we chose TIMP-1shRNA as the target gene fragment and recombinant adenovirus plasmid Adeno-X TM as gene therapy vector and successfully inserted the TIMP-1shRNA gene fragment into the recombinant adenovirus vector.…”

Section: Discussionmentioning

confidence: 99%

Construction and identification of recombinant adenovirus carrying human TIMP-1shRNA gene

et al. 2015

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ABSTRACT. The aim of this study was to construct the recombinant adenovirus carrying human TIMP-1shRNA gene expression system for preliminary identification to lay the foundation for the further study of gene therapy. Using the Adeno-X TM system, the recombinant adenovirus plasmid pAdeno-X TM green fluorescent protein (GFP)-tissue inhibitor of metalloprotease (TIMP)-1 small hairpin (1shRNA) was constructed by including the target gene fragment of the TIMP-1shRNA shuttle plasmid pShuttle2-GFP-TIMP-1shRNA and the backbone plasmid pAdeno-X TM by homologous recombination in Escherichia coli. Recombinant plasmids were transfected into HEK293A cells to package the recombinant adenovirus rvAdeno-X TM GFP-TIMP-1shRNA. The recombinant adenovirus was identified by polymerase chain reaction, and the viral titer and infection efficiency were detected using GFP. Polymerase chain reaction and restriction endonuclease digestion demonstrated that rvAdeno-X TM GFP-TIMP-1shRNA had been successfully constructed, which has a strong ability to infect the kidney. The TIMP-1shRNA adenovirus expression vector was successfully constructed using homologous recombination methods.

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“…Activated myofibroblasts are the primary target for antifibrotic therapy, because a reduction in activated myofibroblasts may lead to a reversal of fibrosis (Brenner 2009;Kisseleva and Brenner 2011). Inactivation of myofibroblasts is also expected to cease fibrosis.…”

Section: Potential Antifibrotic Therapiesmentioning

confidence: 99%

Myofibroblasts: Biochemical and Proteomic Approaches to Fibrosis

Honda

Park

Yoshida

et al. 2013

Tohoku J. Exp. Med.

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Fibrosis is a state, in which excess amounts of extracellular matrix are deposited in the tissue. Fibrosis can occur in various organs, including the liver, lung, kidney and heart. The progression of fibrosis involves interstitial hypercellularity, accumulation of extracellular matrix, and atrophy of epithelial structures, resulting in a loss of normal function. Myofibroblasts play a crucial role in the development and progress of fibrosis. When stimulated, myofibroblasts actively synthesize connective tissue components and cause organ fibrosis. As a result, the process and the mechanism of myofibroblast activation represent a target for antifibrotic treatment. As yet, however, an effective treatment has not been developed, and new treatment modalities are expected. Because activation of myofibroblasts is a key event during fibrosis development, there is great interest in identifying and characterizing proteins whose expression is changed after this activation. In this review, fibrosis is outlined and the role of myofibroblasts in this disorder is described. Furthermore, the search for candidate proteins to target for treatment and the prospects of antifibrotic therapy are discussed.

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Anti-fibrogenic strategies and the regression of fibrosis

Cited by 147 publications

References 115 publications

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Construction and identification of recombinant adenovirus carrying human TIMP-1shRNA gene

Myofibroblasts: Biochemical and Proteomic Approaches to Fibrosis

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