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

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 expos...

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Bibliographic Details
Published in:	In vivo (Athens) Vol. 29; no. 2; pp. 177 - 188
Main Authors:	Pandya, Pinal R, Serra, Virginia, Green, Lora M, Gridley, Daila S
Format:	Journal Article
Language:	English
Published:	Greece 01-03-2015
Subjects:	Animals Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Cell Culture Techniques Cell Line Enzyme Activation - radiation effects Extracellular Matrix - metabolism Female Fibrosis Gene Expression Regulation - radiation effects Immunohistochemistry Integrins - genetics Isoenzymes Models, Animal Photons - adverse effects Protein Kinase C - genetics Protein Kinase C - metabolism Rats Thyroid Gland - metabolism Thyroid Gland - pathology Thyroid Gland - radiation effects calphostin C Proton radiation rodent model FRTL-5 cells extracellular matrix
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1791-7549