%0 Journal Article %A PINAL R. PANDYA %A VIRGINIA SERRA %A LORA M. GREEN %A DAILA S. GRIDLEY %T pKC Modulates Integrin Expression that Contributes to Fibrotic Changes in Irradiated Thyroid Tissue %D 2015 %J In Vivo %P 177-188 %V 29 %N 2 %X Aim: We hypothesized that radiation-induced fibrosis was, in part, a result of altered signal transduction that directly modulates integrin expression and may indirectly affect the extracellular matrix (ECM). Major focus was given on protein kinase C (pKC). Materials and Methods: Rat FRTL-5 and primary thyroid cells were exposed to proton radiation (5 and 10 Gy). Hours to days after exposure, a series of assays were performed. In addition, the neck region of Lewis rats was proton-irradiated to 40 Gy (5 Gy/day or 10 Gy/day). At 11 weeks after exposure, thyroid tissue was evaluated. Results: Accumulation of ECM in irradiated FRTL-5 and primary thyroid cells was coincident with loss of tissue organization and follicularization at one or more doses and time points. Several pKC isoforms increased post-irradiation, which coincided with modulated integrin expression; fibronectin, laminin and collagen were also altered (p<0.05 vs. 0 Gy). Modulation of thyroid cells in culture with 12-O-tetradecanoylphorbol-13-acetate (TPA)±calphostin C supported a direct role of pKC in these altered properties. Thyroid tissue from irradiated rats had significantly more fibrotic lesions and increases in several pKC isoforms, integrins and fibronectin compared to 0-Gy (p<0.05). Conclusion: pKC is a likely contributor to alteration of key players associated with radiation-induced fibrosis. %U https://iv.iiarjournals.org/content/invivo/29/2/177.full.pdf