Narrative review: fibrotic diseases: cellular and molecular mechanisms and novel therapies

J Rosenbloom, SV Castro… - Annals of internal medicine, 2010 - acpjournals.org
J Rosenbloom, SV Castro, SA Jimenez
Annals of internal medicine, 2010acpjournals.org
Abnormal and exaggerated deposition of extracellular matrix is the hallmark of many fibrotic
diseases, including systemic sclerosis and pulmonary, liver, and kidney fibrosis. The
spectrum of affected organs, the usually progressive nature of the fibrotic process, the large
number of affected persons, and the absence of effective treatment pose an enormous
challenge when treating fibrotic diseases. Delineation of the central role of transforming
growth factor-β (TGF-β) and identification of the specific cellular receptors, kinases, and …
Abnormal and exaggerated deposition of extracellular matrix is the hallmark of many fibrotic diseases, including systemic sclerosis and pulmonary, liver, and kidney fibrosis. The spectrum of affected organs, the usually progressive nature of the fibrotic process, the large number of affected persons, and the absence of effective treatment pose an enormous challenge when treating fibrotic diseases. Delineation of the central role of transforming growth factor-β (TGF-β) and identification of the specific cellular receptors, kinases, and other mediators involved in the fibrotic process have provided a sound basis for development of effective therapies. The inhibition of signaling pathways activated by TGF-β represents a novel therapeutic approach for the fibrotic disorders. One of these TGF-β pathways results in the activation of the nonreceptor tyrosine kinase cellular Abelson (c-Abl), and c-Abl inhibitors, including imatinib mesylate, diminishing the fibrogenic effects of TGF-β. Thus, recently acquired basic knowledge about the pathogenesis of the fibrotic process has enabled the development of novel therapeutic agents capable of modifying the deleterious effects of the fibrotic diseases.
acpjournals.org