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Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Wang Zihan[1,2,3] * ; Lei Zhuowei[4] * ; Wang Quanji[1,2,3] ; Jiang Qian[1,2,3] ; Zhang Zhuo[1,2,3] ; Liu Xiaojin[1,2,3] ; Xing Biao[1,2,3] ; Li Sihan[1,2,3] ; Guo Xiang[1,2,3] ; Liu Yanchao[1,2,3] ; Li Xingbo[1,2,3] ; Qi Yiwei[1,2,3] ; Shu Kai[1,2,3] ; Zhang Huaqiu[1,2,3] ; Huang Yimin[1,2,3] ; Lei Ting[1,2,3] ;
单位： [1]Department of Neurosurgery,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China. [2]Sino-German Neuro-Oncology Molecular Laboratory,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China. [3]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China. [4]Department of Orthopedics,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China.
出处：
DOI： 10.7150/ijbs.86736
ISSN：

关键词： Growth hormone-secreting pituitary adenoma Somatostatin Endoplasmic reticulum stress Connexin 36 Gap junctions Quinine

摘要：
Somatostatin analogues (SSTA) are first-line pharmacological treatment choice for acromegaly, which received satisfying tumor shrinkage and normalization of growth hormone. However, there are still patients unresponsive to SSTA, and the underline mechanism remains unknown. Besides, there is no evidence regarding the role of endoplasmic reticulum stress (ERS) and its transmission in SSTA resistance, which also require investigation. Primary growth hormone adenoma cells and cell lines were treated with SSTA; autophagy double-labeled LC3 (mRFP-GFP) adenovirus transfection, flow cytometry sorting, western blotting, calcium imaging as well as immunofluorescence staining were used to determine ERS and autophagy signal transmission; xenograft and syngeneic tumor in vivo model were exploited to confirm the ERS signal transmission mediated effect. Our results revealed that SSTA induces ERS in pituitary growth hormone (GH) adenoma cells. The ERS signals can be intercellularly transmitted, leading to less responsible to SSTA treatment. Moreover, SSTA stimulates inositol triphosphate (IP3) elevation, mediating ERS intercellular transfer. In addition, connexin 36 tunnels ERS transmission, and its blocker, Quinine, exhibits a synergistic effect with SSTA treating GH adenoma. Our study provided insight into ERS intercellular transmission mediated SSTA resistance, which could be translated into clinical usage to improve SSTA efficiency in GH adenoma treatment.© The author(s).

基金：
This work was supported by the National Natural Science Foundation of China (Grant No. 82173136, No. 82203683).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 生化与分子生物学
JCR分区：
出版当年[2022]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]Department of Neurosurgery,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China. [2]Sino-German Neuro-Oncology Molecular Laboratory,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China. [3]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Neurosurgery,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China. [2]Sino-German Neuro-Oncology Molecular Laboratory,Tongji hospital of Tongji medical college of Huazhong University of Science and Technology,Wuhan,430030,China. [3]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.
推荐引用方式(GB/T 7714)：
Wang Zihan,Lei Zhuowei,Wang Quanji,et al.Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma[J].INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES.2024,20(2):801-817.doi:10.7150/ijbs.86736.
APA：
Wang Zihan,Lei Zhuowei,Wang Quanji,Jiang Qian,Zhang Zhuo...&Lei Ting.(2024).Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,20,(2)
MLA：
Wang Zihan,et al."Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 20..2(2024):801-817

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