Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's - derived fibroblasts
2011

Cyclic AMP Reduces Myofibroblast Formation in Dupuytren's Disease

Sample size: 6 publication Evidence: moderate

Author Information

Author(s): Satish Latha, Gallo Phillip H, Baratz Mark E, Johnson Sandra, Kathju Sandeep

Primary Institution: Center for Genomic Sciences, Allegheny-Singer Research Institute, Pittsburgh, PA, USA

Hypothesis

Increasing the activation of the cyclic AMP signaling pathway will inhibit TGF-β1-induced ECM synthesis and myofibroblast formation.

Conclusion

Increasing cAMP levels shows potential to inhibit the formation of myofibroblasts and accumulation of ECM components.

Supporting Evidence

  • Basal mRNA expression levels of ECM proteins were significantly increased in Dupuytren-derived fibroblasts.
  • Forskolin inhibited the TGF-β1 stimulation of α-SMA mRNA and protein.
  • Forskolin reduced the TGF-β1 induction of fibronectin mRNA and protein.
  • Forskolin inhibited the TGF-β1 induction of CTGF mRNA in PF- and DC-derived cells.
  • Forskolin reduced the TGF-β1 stimulation of Type I and Type III collagen.

Takeaway

This study found that a substance called cyclic AMP can help stop certain cells from turning into myofibroblasts, which are involved in a hand condition called Dupuytren's contracture.

Methodology

Fibroblasts from Dupuytren's contracture and normal palmar fascia were treated with TGF-β1 and forskolin, followed by RNA and protein analysis.

Limitations

The study does not directly identify the precise mechanisms by which increased cAMP levels inhibit myofibroblast formation.

Participant Demographics

Fibroblasts were derived from patients with Dupuytren's contracture and normal palmar fascia.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1471-2474-12-113

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication