Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18626
Hemmatazad, H; Maciejewska Rodrigues, H; Maurer, B; Brentano, F; Pileckyte, M; Distler, J H W; Gay, R E; Michel, B A; Gay, S; Huber, L C; Distler, O; Jüngel, A (2009). Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis. Arthritis and Rheumatism, 60(5):1519-1529.
View at publisher
OBJECTIVE: We have recently shown a significant reduction in cytokine-induced transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC-7) as a possible mechanism by which TSA exerts its antifibrotic function. METHODS: Skin fibroblasts from patients with SSc were treated with TSA and/or transforming growth factor beta. Expression of HDACs 1-11, extracellular matrix proteins, connective tissue growth factor (CTGF), and intercellular adhesion molecule 1 (ICAM-1) was analyzed by real-time polymerase chain reaction, Western blotting, and the Sircol collagen assay. HDAC-7 was silenced using small interfering RNA. RESULTS: SSc fibroblasts did not show a specific pattern of expression of HDACs. TSA significantly inhibited the expression of HDAC-7, whereas HDAC-3 was up-regulated. Silencing of HDAC-7 decreased the constitutive and cytokine-induced production of type I and type III collagen, but not fibronectin, as TSA had done. Most interestingly, TSA induced the expression of CTGF and ICAM-1, while silencing of HDAC-7 had no effect on their expression. CONCLUSION: Silencing of HDAC-7 appears to be not only as effective as TSA, but also a more specific target for the treatment of SSc, because it does not up-regulate the expression of profibrotic molecules such as ICAM-1 and CTGF. This observation may lead to the development of more specific and less toxic targeted therapies for SSc.
79 downloads since deposited on 25 May 2009
24 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||25 May 2009 04:48|
|Last Modified:||21 Jun 2014 19:17|
|Additional Information:||The attached file is a preprint (accepted version) of an article published in http://www3.interscience.wiley.com/journal/76509746/home?CRETRY=1&SRETRY=0|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page