期刊
EXPERIMENTAL DERMATOLOGY
卷 19, 期 5, 页码 393-400出版社
WILEY
DOI: 10.1111/j.1600-0625.2010.01082.x
关键词
Fibrosis; connective tissue; hypoxia; growth factor
类别
资金
- BMBF [01 GM 0310]
- Deutsche Forschungsgemeinschaft [EC 140/5-1, SFB829]
Systemic scleroderma may serve as a paradigm for orphan diseases where the rarity, different subsets and fluctuating disease activity constitute major obstacles of research into mechanisms and therapeutic development. Recently, significant advances in the detailed understanding of the functioning of growth factors, their receptors and of the physiology of the connective tissue have been achieved. In particular, an improved concept was developed for the pathophysiology of scleroderma, highlighting the role of hypoxia, cellular stress and a concert of interacting cytokines. Tyrosine kinases have been shown to regulate the activity of a number of cytokines and growth factors, e.g. transforming growth factor-beta and platelet-derived growth factor, which play a central role in the pathophysiology of SSc. Novel pharmacological compounds interacting with signalling cascades induced by hypoxia and intracellular signal transduction pathways of mesenchymal cells, e.g. tyrosine kinase inhibitors, are currently being investigated for the treatment of this life-threatening disease.
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