Vascular alterations upon activation of TGFβ signaling in fibroblasts - implications for systemic sclerosis 英文参考文献.docVIP

Horn and Distler Arthritis Research Therapy 2010,12:125 /content/12/3/125 EDITORIAL Vascular alterations upon activation of TGFβ signaling in ? broblasts - implications for systemic sclerosis Angelika Horn and J?rg HW Distler* See related research by Derrett-Smith et al., /content/12/2/R69 the proliferative vasculopathy is characterized by Abstract prolifera tion of vascular cells with obstruction of the Tissue ?brosis and vascular disease are hallmarks of systemic sclerosis (SSc). Transforming growth factor β (TGFβ) is a key-player in ?broblast activation and tissue ?brosis in SSc. In contrast to ?brosis, evidence for a role of TGFβ in vascular disease of SSc is scarce. Using a transgenic mouse model with ?broblast-speci?c expression of a kinase-de?cient TGFβ receptor type II, Derrett-Smith and colleagues demonstrate that lumen, a? ects larger vessels like the pulmonary arteries and often manifests later in the course of the disease as pulmonary arterial hypertension [2]. e key-role of TGFβ in ? brosis is well established as TGFβ signaling is activated in SSc. Activated TGFβ signaling stimulates the release of collagen in cultured ? broblasts and overexpression of a constitutively active TGFβ receptor type I in ? broblasts results in progressive aberrant TGFβ signaling in ?broblasts might result in activation of vascular smooth muscle cells and architectural changes of the vessel wall of the aorta. ? brosis [3]. Moreover, inhibition of TGFβ signaling exerted potent anti-? brotic e? ects in di? erent pre- clinical models of SSc [4]. In contrast to ? brosis, only few data suggest a role of TGFβ in the vascular pathogenesis of SSc. First data from Using the TβRIIΔk-? b transgenic mouse model, Derrett- mouse models suggest that aberrant TGFβ signaling Smith and colleagues [1] analyzed a potential role of might not result in only ? brosis, but also