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Comment
. 2015 Apr;185(4):909-12.
doi: 10.1016/j.ajpath.2015.01.005. Epub 2015 Feb 14.

ROCK and Rho: Promising therapeutic targets to ameliorate pulmonary fibrosis

David W H Riches  1 , Donald S Backos  2 , Elizabeth F Redente  3
Affiliations
Comment

ROCK and Rho: Promising therapeutic targets to ameliorate pulmonary fibrosis

David W H Riches et al. Am J Pathol. 2015 Apr.

Abstract

This commentary highlights the article by Sisson et al, which establishes the importance of the myocardin-related transcription factor/serum response factor signaling pathway as a therapeutic target in the management of fibrotic lung disease.

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Figures

Figure 1
Figure 1
Fibroblast–myofibroblast differentiation is initiated by environmental factors, such as transforming growth factor (TGF)-β, lysophosphatidic acid (LPA), and mechanotransduction, and is mediated via the Rho-ROCK–myocardin-related transcription factor (MRTF) signaling pathway. These initial signaling events result in the polymerization of G-actin to F-actin and the formation of contractile fibers, a characteristic of myofibroblasts. Polymerization of F-actin frees the transcription factor MRTF, normally sequestered in the cytoplasm by association with G-actin, to translocate to the nucleus, initiating transcription of several profibrotic and antiapoptotic genes. CCG-203971 exerts its antifibrotic effect by inhibiting MRTF nuclear translocation, thereby preventing the up-regulation of gene expression. α-SMA, α smooth muscle actin; Bcl-2, B cell lymphoma 2; FN, fibronectin; PAI-1, plasminogen activator inhibitor-1; SRF, serum response factor; XIAP, X-linked inhibitor of apotosis.
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Comment on

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