Biomarkers in systemic sclerosis.

Systemic sclerosis is an autoimmune inflammatory disorder of unknown etiologycharacterized b y pronounced fibroproliferative alterations in the microvasculature, and frequent cellular and humoral immunity abnormalities, culminating in a severe and often progressive fibrotic process. Numerous biomarkers reflecting the three main pathogenetic mechanisms in systemic sclerosis have been described; however, aside from several disease-specific autoantibodies, other biomarkers have not been thoroughly validated and require further study. Thus, there is an unmet need for validated biomarkers for diagnosis, disease classification, and evaluation of organ involvement and therapeutic response in systemic sclerosis.

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

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-beta (TGF-beta) 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-beta represents a novel therapeutic approach for the fibrotic disorders. One of these TGF-beta 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-beta. 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.

Role of growth factors in the pathogenesis of tissue fibrosis in systemic sclerosis.

The most severe clinical and pathologic manifestations of systemic sclerosis (SSc) are the result of a fibrotic process characterized by the excessive and often progressive deposition of collagen and other connective tissue macromolecules in skin and numerous internal organs. The mechanisms involved in the initiation and progression of the remarkable fibrotic process in SSc remain largely unknown. Extensive recent studies have indicated that a variety of polypeptide growth factors play a crucial role in this process. The most commonly implicated growth factors include transforming growth factor beta (TGF-ß), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Here, the experimental evidence supporting the participation of various growth factors in the pathogenesis of the fibrotic process in SSc and the molecular mechanisms involved will be reviewed.