Fibrosis, or the accumulation of extracellular matrix molecules that make up scar tissue, is a common feature of chronic tissue injury. Pulmonary fibrosis, renal fibrosis, and hepatic cirrhosis are among the more common fibrotic diseases, which in aggregate represent a huge unmet clinical need. New appreciation of the common features of fibrosis that are conserved among tissues has led to a clearer understanding of how epithelial injury provokes dysregulation of cell differentiation, signaling, and protein secretion. At the same time, discovery of tissue-specific features of fibrogenesis, combined with insights about genetic regulation of fibrosis, has laid the groundwork for biomarker discovery and validation, and the rational identification of mechanism-based antifibrotic drugs. Together, these advances herald an era of sustained focus on translating the biology of fibrosis into meaningful improvements in quality and length of life in patients with chronic fibrosing diseases.
"The direct link between inflammation and fibrosis has been well established as well (Wick et al., 2013). Despite many clinical and experimental investigations, effective treatment for fibrosis is still lacking in the clinic (Friedman et al., 2013). FTY720, an S1P analog, effectively inhibits the egress of T and B cells from lymph nodes (Kabashima et al., 2006; Matloubian et al., 2004), thereby reducing the number of antigen-primed/restimulated cells that recirculate to peripheral inflammatory tissues (Brinkmann and Lynch, 2002), and consequently halts inflammation. "
"The example of TGF-β1 hyper-activity in Marfan syndrome demonstrates that inhibition of LTBP binding to the ECM will need to be investigated with care as one possible strategy to prevent TGF-β1 activation in fibrosis. One the ECM side, current strategies aim at generally reducing the crosslink-degree which contributes to both, scar stiffening and binding of LTBP-1; targets are transglutaminases, lysyl oxidases, lysyl oxidase-like enzymes, and lysyl hydroxylases (reviewed in   ). Proteoglycans, in particular heparin/heparan sulfate are other attractive targets in the ECM due to their mediating role between different fibrillar ECM proteins as well as LTBPs   . "
"Current treatments of tissue fibrosis mostly rely on targeting the inflammatory response; however, these are ultimately ineffective in preventing progression of the disease, underscoring the need for new mechanistic insights and therapeutic approaches (Friedman et al, 2013). Recent studies indicate the involvement of miRNAs in pulmonary fibrosis (Pandit et al, 2011). "
[Show abstract][Hide abstract] ABSTRACT: Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis.
EMBO Molecular Medicine 09/2014; 6(10). DOI:10.15252/emmm.201303604 · 8.67 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.