Delivery of Sonic Hedgehog Gene Repressed Irradiation-induced Cellular Senescence in Salivary Glands by Promoting DNA Repair and Reducing Oxidative Stress

Theranostics
Bo HaiFei Liu

Abstract

Rationale: Irreversible hypofunction of salivary glands or xerostomia is common in head and neck cancer survivors treated with radiotherapy even when various new techniques are applied to minimize the irradiation (IR) damage. This condition severely impairs the quality of life of patients and can only be temporarily relieved with current treatments. We found recently that transient expression of Sonic Hedgehog (Shh) in salivary glands after IR rescued salivary function, but the underlying mechanisms are not totally clear. Methods: We generated a mouse model of IR-induced hyposalivation, and delivered adenoviral vectors carrying Shh or control GFP gene into submandibular glands (SMGs) via retrograde ductal instillation 3 days after IR. The cellular senescence was evaluated by senescence-associated beta-galactosidase assay and the expression of senescence markers. The underlying mechanisms were explored by examining DNA damage, oxidative stress, and the expression of related genes by qRT-PCR, Western blot and immunofluorescent staining. Results: Shh gene transfer repressed IR-induced cellular senescence by promoting DNA repair and decreasing oxidative stress, which is mediated through upregulating expression of genes related to D...Continue Reading

Citations

Jul 25, 2019·Journal of Dental Research·M H AureM P Hoffman
Jul 30, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Chen WangJin-Wen Xu
Nov 2, 2018·International Journal of Molecular Sciences·Muhammad Shahnawaz SoyfooChristine Delporte
Jun 6, 2020·Antioxidants·Ana Martin-HurtadoFrancesc R Garcia-Gonzalo
Jul 8, 2020·Cells·Claudia D'AgostinoChristine Delporte
Dec 17, 2020·Cancer Research·Robert P Coppes
Jan 10, 2021·Experimental Gerontology·Huan LiuYan Li
Aug 29, 2021·Biochemical and Biophysical Research Communications·Jiao DongHideharu Hibi

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