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Increased Expression of Connective Tissue Growth Factor (CTGF) in Multiple Organs After Exposure of Non-Human Primates (NHP) to Lethal Doses of Radiation

Zhang, Pei*; Cui, Wanchang*†; Hankey, Kim G.*; Gibbs, Allison M.*; Smith, Cassandra P.*; Taylor-Howell, Cheryl*; Kearney, Sean R.*; MacVittie, Thomas J.*†

doi: 10.1097/HP.0000000000000343
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Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus, and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition, respectively, suggesting possible crosstalk between spleen and other organs. These data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs.

*Department of Radiation Oncology, University of Maryland School of Medicine, 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201.

The authors declare no conflicts of interest.

For correspondence contact: Wanchang Cui, Department of Radiation Oncology, University of Maryland School of Medicine, 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201, or email at wcui@som.umaryland.edu; or Thomas MacVittie, University of Maryland, School of Medicine, Department of Radiation Oncology, 10 South Pine Street, MSTF 6-34E, Baltimore, MD 21201, or email at tmacvittie@som.umaryland.edu.

(Manuscript accepted 24 June 2015)

© 2015 by the Health Physics Society