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  • pKC modulates integrin expression that contributes to fibrotic changes in irradiated thyroid tissue.

pKC modulates integrin expression that contributes to fibrotic changes in irradiated thyroid tissue.

In vivo (Athens, Greece) (2015-03-21)
Pinal R Pandya, Virginia Serra, Lora M Green, Daila S Gridley
ABSTRACT

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). 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. 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). pKC is a likely contributor to alteration of key players associated with radiation-induced fibrosis.

MATERIALS
Product Number
Brand
Product Description

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Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
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Tris(2-pyridylmethyl)amine, 98%
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Propidium iodide solution, solution (1.0 mg/ml in water)