What is important to target fibrosis: location, location, location! of cold-shock proteins

Excerpt

Regardless of its pathogenesis, the main aspect of organ fibrosis is excessive extracellular interstitial collagen deposition. The tissue cicatrization eventually results in loss of function. The highlighted article by Higashi et al. describes that taking a long visionary way may eventually succeed, always keeping in mind the quest to counteract fibrogenesis as common outcome of chronic inflammatory diseases. The group of researchers from the Osaka University in Japan were eager to identify pathways related to fibrotic transforming growth factor-β activities [1, 2]. On their path they identified cold-shock proteins, especially Y-box (YB) protein-1, as an interrogator of Smad3 signaling. Given that collagen type I is a target gene of YB-1, which is suppressed in its expression [1], they went on to develop a synthetic compound to interfere with YB-1 activities. The rationale of the compound denoted HSc025 was to release cytoplasmic YB-1 from the cytoplasm and force it into the nuclear compartment. The putative anti-fibrotic activity of this approach was tested in an animal model of CCl₄-induced hepatic fibrosis. Mice receiving the small synthetic compound exhibited reduced collagen synthesis and intactness of the liver histological architecture. Thus, the targeting of cold-shock proteins seems to be a promising approach to combat pro-fibrotic processes. …