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J Cell Biochem. 2005 May 15;95(2):256-67.

TGF-beta induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C betaII activation in vitro.

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Institute of Anatomy and Cell Biology, School of Medicine, Yang-Ming University, Taipei, Taiwan.


Graves' ophthalmopathy is accompanied by hyaluronan (HA) accumulation in the orbital space and infiltration of immunocompetent cells and cytokines, including IFN-gamma, IL-1beta, and TGF-beta. We examined the signal transduction pathways by which TGF-beta induces HA synthesis in normal orbital fibroblasts, orbital fibroblasts from patients with Graves' ophthalmopathy, and abdominal fibroblasts. Calphostin C inhibited the stimulation of HA synthesis by TGF-beta. Phorbol 12-myristate 13-acetate (PMA) activation of PKC stimulated HA production. The effects of TGF-beta and PMA were not synergistic. Stimulation by TGF-beta and PMA were dependent on protein synthesis and their effects were inhibited by cycloheximide. Since TGF-beta-induced HA synthesis was inhibited by BAPTA or by PKC inhibitors, a calcium-dependent PKC was most likely involved. The PKA inhibitor H-89 enhanced TGF-beta- and PMA-induced HA synthesis, thus showing that communication between the PKA and PKC pathways was evident. TGF-beta stimulated the translocation of PKCbetaII to the cell membrane. PKCbetaII, a key enzyme in the regulation of HA synthesis by TGF-beta, might be an appropriate target for therapeutic compounds to be used to treat Graves' ophthalmopathy accompanied by inflammation.

[Indexed for MEDLINE]

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