Global expression analysis of the fibroblast transcriptional response to TGFbeta.
OBJECTIVE
Transforming Growth Factor-beta (TGFbeta) is the predominant cytokine in all forms of fibrotic reactions. As well as being secreted by immune modulators of fibrosis such as macrophages, it is involved in an autocrine feedback loop of fibroblast stimulation whose regulation is still poorly understood. We wished to gain some insight into the mechanisms of the fibroblast response to TGFbeta.


METHODS
We undertook an exhaustive transcript profiling experiment using a widely validated restriction enzyme based method for identifying differentially expressed genes (GeneCalling). Transcriptional responses throughout a 24-hour time course were examined at multiple time points and classified.


RESULTS
By 24 hours of TGF treatment over 1000 bands, representing a large number of transcripts, were down- or upregulated greater than 2-fold. All of the known genes responsive to TGFbeta, such as collagen and connective tissue growth factor, were upregulated.


CONCLUSIONS
This encyclopedic method revealed many unknown transcriptional responses to TGFbeta including the upregulation of a variety of less expected cytoskeletal and matrix components, as well as interactions between the TGFbeta and tumor necrosis factor (TNF) pathways and alterations in cell death-related pathways. These may in part explain the idiosyncratic responses of mesenchymal cells to TGFbeta.
Gardner
H
H
Biogen Inc, Cambridge, Massachusetts, USA.
Strehlow
D
D
Bradley
L
L
Widom
R
R
Farina
A
A
de Fougerolles
A
A
Peyman
J
J
Koteliansky
V
V
Korn
J H
JH
D018929:Cell Culture Techniques; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha