Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress

被引:0
|
作者
Hu, Meijun [1 ]
Hu, Liang [2 ]
Yang, Tao [2 ]
Zhou, Bowen [2 ]
Feng, Xuanhe [2 ]
Fan, Zhipeng [1 ]
Shan, Zhaochen [2 ]
机构
[1] Capital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
[2] Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R China
基金
中国国家自然科学基金;
关键词
ionizing radiation; Hedgehog pathway; salivary gland (SG) injury; oxidative stress; microvessel; NECK-CANCER-PATIENTS; SONIC HEDGEHOG; INDUCED HYPOSALIVATION; CELLULAR SENESCENCE; XEROSTOMIA; HEAD; HYPOFUNCTION; DELIVERY; THERAPY;
D O I
10.3390/antiox13080904
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).
引用
收藏
页数:17
相关论文
共 50 条
  • [21] Liensinine alleviates mouse intestinal injury induced by sepsis through inhibition of oxidative stress, inflammation, and cell apoptosis
    Wang, Guanglu
    Ma, Fenfen
    Xie, Kunmei
    Li, Xueqing
    Tan, Xuelian
    Xia, Yan
    Wang, Yan
    Dong, Jingquan
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2024, 127
  • [22] Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation
    Zhang, Weixin
    Yin, Lianhong
    Tao, Xufeng
    Xu, Lina
    Zheng, Lingli
    Han, Xu
    Xu, Youwei
    Wang, Changyuan
    Peng, Jinyong
    ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2016, 45 : 193 - 201
  • [23] Magnesium isoglycyrrhizinate alleviates fructose-induced liver oxidative stress and inflammatory injury through suppressing NOXs
    Yang, Yan-Zi
    Liu, Zhi-Hong
    Wang, Shan-Chun
    Zhang, Xi-Quan
    Xu, Hong-Jiang
    Yang, Ling
    Kong, Ling-Dong
    EUROPEAN JOURNAL OF PHARMACOLOGY, 2020, 883
  • [24] Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid Metabolism and Oxidative Stress
    Nagappan, Arulkumar
    Jung, Dae Young
    Kim, Ji-Hyun
    Lee, Hoyoung
    Jung, Myeong Ho
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (09)
  • [25] Royal jelly acid alleviates diet-induced hyperlipidemia through regulation of oxidative stress and tryptophan metabolism
    Zhi, Dan-dan
    He, Xi-ying
    Yang, Lin-fu
    Xue, Yun-fei
    Liu, Yi-qiu
    Yue, Dan
    Feng, Yi-nan
    Dong, Kun
    Tian, Ya-kai
    EUROPEAN JOURNAL OF PHARMACOLOGY, 2025, 998
  • [26] Fatty aldehyde dehydrogenase - Potential role in oxidative stress protection and regulation of its gene expression by insulin
    Demozay, D
    Rocchi, S
    Mas, JC
    Grillo, S
    Pirola, L
    Chavey, C
    Van Obberghen, E
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (08) : 6261 - 6270
  • [27] Protective effects of melatonin against 12C6+ beam irradiation-induced oxidative stress and DNA injury in the mouse brain
    Wu, Z. H.
    Zhang, H.
    Wang, X. Y.
    Yang, R.
    Liu, B.
    Liu, Y.
    Zhao, W. P.
    Feng, H. Y.
    Xue, L. G.
    Hao, J. F.
    Niu, B. T.
    Wang, Z. H.
    ADVANCES IN SPACE RESEARCH, 2012, 49 (01) : 196 - 203
  • [28] Trehalose attenuates spinal cord injury through the regulation of oxidative stress, inflammation and GFAP expression in rats
    Nazari-Robati, Mahdieh
    Akbari, Mahboobe
    Khaksari, Mohammad
    Mirzaee, Moghaddameh
    JOURNAL OF SPINAL CORD MEDICINE, 2019, 42 (03): : 387 - 394
  • [29] NDUFS3 alleviates oxidative stress and ferroptosis in sepsis induced acute kidney injury through AMPK pathway
    Wang, YuChen
    Lv, WuYang
    Ma, XiaoTong
    Diao, RuXue
    Luo, XiaoXiao
    Shen, QiuLing
    Xu, MingYu
    Yin, MengJiao
    Jin, YingYu
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2024, 143
  • [30] Recombinant Adenovirus siRNA Knocking Down the Ndufs4 Gene Alleviates Myocardial Apoptosis Induced by Oxidative Stress Injury
    Wang, Beibei
    Zhang, Jinsheng
    Xu, Aijun
    CARDIOLOGY RESEARCH AND PRACTICE, 2023, 2023