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Survivin, the novel target for the treatment of fibrotic disease

     A fibroblast is a type of mesenchymal cells that synthesize the extracellular matrix(ECM) and collagen, and plays a key role in wound healing by differentiating into alpha-smooth muscle actin expressing myofibroblasts. At last, the normal wound repair progress following injury requires the elimination of myofibroblasts by apoptosis. However, in abnormal state, this excessive ECM can result in the progressive destruction of tissue architecture and lead to impaired organ function. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of lung disease caused by fibrosis of the lungs.

     Studies have indicated that normal lung fibroblasts have basal resistance to Fas-mediated apoptosis that can be overcome in the treatment of cycloheximide 60 (CHX), an inhibitor of protein translation, or by exposure to TNF-alpha and interferon-gamma. On the other hand, endothelin-1(ET-1) and TGF-beta1 are also been found to independently increase myofibroblast resistance to apoptosis induced by the combination of Fas-activation and CHX (Fas/CHX) through activation of PI3K/AKT[1].
     In the newest paper, Horowitz et al. Reported their findings about the role of FAK and the relationship between FAK and PI3K/AKT in the regulation of myofibroblast 84 resistance to apoptosis by ET-1. The results showed that ET-1 regulated myofibroblast survival by Rho/ROCK-dependent activation of FAK. Further mechanism studies suggested that the anti-apoptotic effects of FAK are dependent on activation of PI3K/AKT and the subsequent increased expression of Survivin[2].
     Taken together, Survivin may play an important role in fibrosis by promoting myofibroblast survival and thus Survivin may be a novel target for the treatment of fibrotic disease.


References
[1]. Am J Respir Cell Mol Biol 724 2009;41:484–93. 725.
[2]. Int J Biochem Cell Biol (2011), doi:10.1016/j.biocel.2011.10.011.