title: pKC modulates integrin expression that contributes to fibrotic changes in irradiated thyroid tissue.
abstract: OBJECTIVE
  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).
  
  
  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).
  
  
  CONCLUSIONS
  pKC is a likely contributor to alteration of key players associated with radiation-induced fibrosis.
authors: Department of Basic Sciences, Divisions of Microbiology and Radiation Research Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors: Pinal R
authors: PR
authors: Pandya
authors: Department of Basic Sciences, Divisions of Microbiology and Radiation Research Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors: Virginia
authors: V
authors: Serra
authors: Department of Basic Sciences, Divisions of Microbiology and Radiation Research Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors: Lora M
authors: LM
authors: Green
authors: Department of Basic Sciences, Divisions of Microbiology and Radiation Research Loma Linda University School of Medicine, Loma Linda, CA, U.S.A. dgridley@llu.edu.
authors: Daila S
authors: DS
authors: Gridley
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D004789:Enzyme Activation / Q000528:radiation effects; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000528:radiation effects; D007150:Immunohistochemistry; D016023:Integrins / Q000235:genetics*; D007527:Isoenzymes; D023421:Models, Animal; D017785:Photons / Q000009:adverse effects; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects
chemical_list: D015815:Cell Adhesion Molecules; D016023:Integrins; D007527:Isoenzymes; D011493:Protein Kinase C
keywords: FRTL-5 cells; Proton radiation; calphostin C; extracellular matrix; rodent model