| The cause of ?brotic disease is unknown. We have undertaken
transcriptional pro?ling of
dermal ?broblasts cultured from patients with the ?brotic disease scleroderma
(systemic sclerosis, SSc)
to identify genes overexpressed in ?brosis and have explored their contribution
to the ?brotic phenotype.
Connective tissue growth factor (CTGF, CCN2), a member of the CCN family
of proteins, is
overexpressed in SSc ?broblasts. In adult skin, CTGF is not normally expressed
in dermal ?broblasts.
However, CTGF is induced during the wound healing response and is constitutively
overexpressed by
?broblasts present in ?brotic lesions. The overexpression of CTGF present
in ?brotic lesions contributes
to the phenotype of scleroderma in that CTGF promotes matrix deposition,
and ?broblast adhesion
and proliferation. In animal models, whereas either TGFb or CTGF alone
produce only a transient
?brotic response, CTGF and TGFb act together to promote sustained ?brosis.
Thus the constitutive
overexpression of CTGF by ?broblasts present in ?brotic lesions would be
expected to directly contribute
to chronic, persistent ?brosis. (Keio J Med 53 (2): 74?77, June 2004) |
