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- Title
Scleroderma Fibroblasts Demonstrate Enhanced Activation of Akt (Protein Kinase B)In Situ.
- Authors
Jun, Jae-Bum; Kuechle, Melanie; Min, Junki; Shim, Seung Cheol; Kim, Giok; Montenegro, Vivianne; Korn, Joseph H.; Elkon, Keith B.
- Abstract
Recent studies suggest that, in addition to activation and hypersecretion of matrix components, fibroblasts from patients with systemic sclerosis (SSc) are relatively resistant to apoptosis. Transforming growth factor-β (TGF)-β is strongly implicated in the pathogenesis of SSc and we and others have shown that TGF-β can activate Akt, a kinase with potent anti-apoptotic effects. To determine whether Akt was activated in SSc, we quantified phospho-Akt expression in skin fibroblastsin vitroby western blot analysis and a functional kinase assay. In addition, the relative proportion of fibroblasts containing activated Akt in was quantified by immunohistochemistry on skin sectionsinsitu. Analysis of Akt phosphorylation of skin fibroblastsin vitrosuggested increased phosphorylation of Akt, and evaluation of skin sections by immunohistochemistry revealed significantly higher percentages of fibroblasts that stained for phospho-Akt compared with controls (78%±14.0%vs13%±9%, p<0.001). In addition, co-incident staining of phospho-Akt andα-smooth muscle actin was observed in some fibroblasts. These findings indicate that Akt is activatedinsituin skin fibroblasts from patients with SSc. Akt activation may contribute to resistance to apoptosis, selection of disease-inducing fibroblasts, and, possibly, myofibroblasts.
- Subjects
FIBROBLASTS; CONNECTIVE tissue cells; APOPTOSIS; GROWTH factors; CYTOKINES; CHEMICAL reactions
- Publication
Journal of Investigative Dermatology, 2005, Vol 124, Issue 2, p298
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/j.0022-202X.2004.23559.x