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
  • [41] Gender segregation in gene expression and vulnerability to oxidative stress induced injury in ventral mesencephalic cultures of dopamine neurons
    Tao, Qingqing
    Fan, Xiaolan
    Li, Ting
    Tang, Yu
    Yang, Dehua
    Le, Weidong
    JOURNAL OF NEUROSCIENCE RESEARCH, 2012, 90 (01) : 167 - 178
  • [42] Carnosine and crocin ameliorate oxidative stress in rats with rhabdomyolysis-induced acute kidney injury through upregulating HO-1 gene expression
    El-Ashmawy, Nahla E.
    Khedr, Eman G.
    Doghish, Ahmed S.
    Elballal, Mohammed S.
    FOOD BIOSCIENCE, 2022, 49
  • [43] AZT-induced mitochondrial toxicity: an epigenetic paradigm for dysregulation of gene expression through mitochondrial oxidative stress
    Koczor, Christopher A.
    Jiao, Zhe
    Fields, Earl
    Russ, Rodney
    Ludaway, Tomika
    Lewis, William
    PHYSIOLOGICAL GENOMICS, 2015, 47 (10) : 447 - 454
  • [44] Carfilzomib-induced cardiotoxicity mitigated by dexrazoxane through inhibition of hypertrophic gene expression and oxidative stress in rats
    Al-Harbi, Naif O.
    TOXICOLOGY MECHANISMS AND METHODS, 2016, 26 (03) : 189 - 195
  • [45] Oxidative stress suppresses dexamethasone-induced gene expression through inhibition of glucocorticoid receptor nuclear translocation
    Xu, Haishan
    Chu, Shijian
    FASEB JOURNAL, 2008, 22
  • [46] Penthorum Chinense Pursh Extract Alleviates Aflatoxin B1-Induced Liver Injury and Oxidative Stress Through Mitochondrial Pathways in Broilers
    Nabi, Fazul
    Tao, Weilai
    Ye, Ruiling
    Li, Zhenzhen
    Lu, Qin
    Shang, Yangfei
    Hu, Yu
    Fang, Jiali
    Bhutto, Zohaib Ahmed
    Liu, Juan
    FRONTIERS IN VETERINARY SCIENCE, 2022, 9
  • [47] Thyroid hormone-induced oxidative stress in rodents and humans:: A comparative view and relation to redox regulation of gene expression
    Fernández, V
    Tapia, G
    Varela, P
    Romanque, P
    Cartier-Ugarte, D
    Videla, LA
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, 2006, 142 (3-4): : 231 - 239
  • [48] POLYAMINE ACCLIMATION ALLEVIATES HYPERSALINITY-INDUCED OXIDATIVE STRESS IN A MARINE GREEN MACROALGA, ULVA FASCIATA, BY MODULATION OF ANTIOXIDATIVE ENZYME GENE EXPRESSION
    Sung, Ming-Shiuan
    Chow, Te-Jin
    Lee, Tse-Min
    JOURNAL OF PHYCOLOGY, 2011, 47 (03) : 538 - 547
  • [49] Elemene mitigates oxidative stress and neuronal apoptosis induced by cerebral ischemia-reperfusion injury through the regulation of glutathione metabolism
    Wu, Pu
    Cheng, Long-Hui
    Liu, Yan-Lei
    Zhang, Jiu-Long
    Dong, Xue-Man
    Chen, Lin
    Xu, Yu-Xin
    Ren, Ying-Ying
    Zhang, Hua-Min
    Liu, Zhao-Qian
    Zhou, Jian-Liang
    Xie, Tian
    JOURNAL OF ETHNOPHARMACOLOGY, 2025, 340
  • [50] Anthraquinones Extract from Morinda angustifolia Roxb. Root Alleviates Hepatic Injury Induced by Carbon Tetrachloride through Inhibition of Hepatic Oxidative Stress
    Chen Rui-rong
    Liu Juan
    Chen Zhe
    Cai Wen-jun
    Li Xiu-fen
    Lu Chuan-li
    EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2020, 2020