Tissue
fibrosis is a common cause of organ failure. Consequently, elucidation of the mechanisms underlying both the initiation and progression of
fibrosis is an essential step toward establishing new therapeutic strategies for the treatment of organ failure. Fibroblasts are the principal effectors mediating
fibrosis and their heterogeneous origins, including epithelial-mesenchymal transition (EMT), bone marrow-derived cell or fibrocyte, and endothelial-mesenchymal transition (EndMT), have been demonstrated. Chronic
hypoxia has been proposed as an important microenvironmental factor in the development of tissue
fibrosis. Recently, we reported that
hypoxia induces EMT in renal tubular epithelial cells through activation of
hypoxia-inducible factor-1alpha (HIF-1alpha). Using the Cre-loxP mediated gene targeting of HIF-1alpha or VHL which acts as a
ubiquitin ligase to promote degradation of HIF-1alpha, we showed that HIF-1alpha plays a key role in the progression of renal
fibrosis. As a large number of molecules that contribute to the induction of
fibrosis have been identified, and their signal transduction pathway has been characterized, these
fibrosis-related molecules have been proposed as therapeutic targets. EMT antagonists,
TGF-beta signal modulator, and HIF-1alpha inhibitor could be useful for the treatment of
fibrosis.