4 research outputs found
Mechanical Tension Increases CCN2/CTGF Expression and Proliferation in Gingival Fibroblasts via a TGFβ-Dependent Mechanism
Unlike skin, oral gingival do not scar in response to tissue injury. Fibroblasts,
the cell type responsible for connective tissue repair and scarring, are exposed
to mechanical tension during normal and pathological conditions including wound
healing and fibrogenesis. Understanding how human gingival fibroblasts respond
to mechanical tension is likely to yield valuable insights not only into
gingival function but also into the molecular basis of scarless repair.
CCN2/connective tissue growth factor is potently induced in fibroblasts during
tissue repair and fibrogenesis. We subjected gingival fibroblasts to cyclical
strain (up to 72 hours) using the Flexercell system and showed that CCN2 mRNA
and protein was induced by strain. Strain caused the rapid activation of latent
TGFβ, in a fashion that was reduced by blebbistatin and FAK/src inhibition,
and the induction of endothelin (ET-1) mRNA and protein expression. Strain did
not cause induction of α-smooth muscle actin or collagen type I mRNAs
(proteins promoting scarring); but induced a cohort of pro-proliferative mRNAs
and cell proliferation. Compared to dermal fibroblasts, gingival fibroblasts
showed reduced ability to respond to TGFβ by inducing fibrogenic mRNAs;
addition of ET-1 rescued this phenotype. Pharmacological inhibition of the
TGFβ type I (ALK5) receptor, the endothelin A/B receptors and FAK/src
significantly reduced the induction of CCN2 and pro-proliferative mRNAs and cell
proliferation. Controlling TGFβ, ET-1 and FAK/src activity may be useful in
controlling responses to mechanical strain in the gingiva and may be of value in
controlling fibroproliferative conditions such as gingival hyperplasia;
controlling ET-1 may be of benefit in controlling scarring in response to injury
in the skin