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Keratinocyte Growth Factor-1 Protects Radioiodine-Induced Salivary Gland Dysfunction in Mice

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  • Jeong Mi Kim

    (Translational Research Center, Inha University, Incheon 22332, Korea
    Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon 22332, Korea
    Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, Incheon 22332, Korea)

  • Mi Eun Choi

    (Translational Research Center, Inha University, Incheon 22332, Korea
    Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, Incheon 22332, Korea)

  • Seok-Ki Kim

    (Department of Nuclear Medicine, National Cancer Center, Goyang 10408, Korea)

  • Ji Won Kim

    (Translational Research Center, Inha University, Incheon 22332, Korea
    Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, Incheon 22332, Korea)

  • Young-Mo Kim

    (Translational Research Center, Inha University, Incheon 22332, Korea
    Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, Incheon 22332, Korea)

  • Jeong-Seok Choi

    (Translational Research Center, Inha University, Incheon 22332, Korea
    Department of Otorhinolaryngology-Head and Neck Surgery, Inha University College of Medicine, Incheon 22332, Korea)

Abstract

Background: Most patients with thyroid cancer suffer from salivary gland (SG) dysfunctions after radioiodine (RI) therapy. We investigated the effects of keratinocyte growth factor (KGF)-1 on RI-induced SG dysfunction in an animal model. Methods: Six C57BL/6 mice were assigned to each of the following groups: treatment naïve control group, RI group, and RI+KGF-1 group. Body and SG weights, salivary flow rates, salivary lag times and changes in 99mTc pertechnetate uptake and excretion were measured, and histologic changes were noted. Amylase activities and epidermal growth factor (EGF) concentrations in saliva were also measured. In addition, TUNEL assays were performed and apoptosis-related protein expressions were assessed. Results: RI-induced reductions in salivary flow rates and increases in salivary lag times observed in the RI group were not observed in RI+KGF-1 group. Mice in RI group had higher HIF1a levels than controls, but HIF1a levels in RI+KGF-1 group were similar to those in control group. Furthermore, mice in RI+KGF-1 group had more mucin stained acini and decreased periductal fibrosis than mice in RI group, and tissue remodeling of many salivary epithelial cells (AQP5) and endothelial cells (CD31) were observed in RI+KGF-1 group. Amylase activity and expression in saliva were greater in RI+KGF-1 group than in RI group, and fewer apoptotic cells were observed in RI+KGF-1 group. Furthermore, BCLxl (anti-apoptotic) expression was higher, and Bax (pro-apoptotic) expression was lower in RI+KGF-1 group than in RI group. Conclusions: Local delivery of KGF-1 might prevent RI-induced SG damage by reducing apoptosis.

Suggested Citation

  • Jeong Mi Kim & Mi Eun Choi & Seok-Ki Kim & Ji Won Kim & Young-Mo Kim & Jeong-Seok Choi, 2020. "Keratinocyte Growth Factor-1 Protects Radioiodine-Induced Salivary Gland Dysfunction in Mice," IJERPH, MDPI, vol. 17(17), pages 1-9, August.
    • Handle: RePEc:gam:jijerp:v:17:y:2020:i:17:p:6322-:d:406414
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    Cited by:

    1. Marit H. Aure & Jennifer M. Symonds & Carlos U. Villapudua & Joshua T. Dodge & Sabine Werner & Wendy M. Knosp & Matthew P. Hoffman, 2023. "FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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