Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress
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作者:
Hu, Meijun
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Capital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
Hu, Meijun
[1
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Hu, Liang
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Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
Hu, Liang
[2
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Yang, Tao
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Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
Yang, Tao
[2
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Zhou, Bowen
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Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
Zhou, Bowen
[2
]
Feng, Xuanhe
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Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
Feng, Xuanhe
[2
]
Fan, Zhipeng
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Capital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
Fan, Zhipeng
[1
]
Shan, Zhaochen
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Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R ChinaCapital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
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
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).
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King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh, Saudi ArabiaKing Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh, Saudi Arabia
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Lasbela Univ Agr Water & Marine Sci, Fac Vet & Anim Sci, Dept Poultry Sci, Uthal, PakistanSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Nabi, Fazul
Tao, Weilai
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Tao, Weilai
Ye, Ruiling
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Ye, Ruiling
Li, Zhenzhen
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Li, Zhenzhen
Lu, Qin
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Lu, Qin
Shang, Yangfei
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Shang, Yangfei
Hu, Yu
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Hu, Yu
Fang, Jiali
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Fang, Jiali
Bhutto, Zohaib Ahmed
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Lasbela Univ Agr Water & Marine Sci, Fac Vet & Anim Sci, Dept Poultry Sci, Uthal, PakistanSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Bhutto, Zohaib Ahmed
Liu, Juan
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Southwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
Univ Vet Sci Engn Res Ctr Chongqing, Chinese Vet Herbal Drugs Innovat Res Lab, Chongqing, Peoples R China
Southwest Univ, Immunol Res Ctr, Med Res Inst, Chongqing, Peoples R ChinaSouthwest Univ, Dept Tradit Chinese Vet Med, Coll Vet Med, Chongqing, Peoples R China
机构:
Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R China
Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Wu, Pu
Cheng, Long-Hui
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Cheng, Long-Hui
Liu, Yan-Lei
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Shanghai Jiao Tong Univ, Inst Nano Biomed & Engn, Shanghai Engn Res Ctr Intelligent Diag & Treatment, Sch Elect Informat & Elect Engn,Dept Instrument Sc, Shanghai 200240, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Liu, Yan-Lei
Zhang, Jiu-Long
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Fudan Univ, Shanghai Publ Hlth Clin Ctr, Dept Radiol, Shanghai 201508, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Zhang, Jiu-Long
Dong, Xue-Man
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R China
Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Dong, Xue-Man
Chen, Lin
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Chen, Lin
Xu, Yu-Xin
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Xu, Yu-Xin
Ren, Ying-Ying
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Ren, Ying-Ying
Zhang, Hua-Min
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Zhang, Hua-Min
Liu, Zhao-Qian
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Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Liu, Zhao-Qian
Zhou, Jian-Liang
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Zhou, Jian-Liang
Xie, Tian
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Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China
Hangzhou Normal Univ, Collaborat Innovat Ctr Tradit Chinese Med Zhejiang, Key Lab Elemene Class Anticanc Chinese Med, Engn Lab Dev & Applicat Tradit Chinese Med, Hangzhou 311121, Zhejiang, Peoples R ChinaHangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China