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aquaporin 9 is involved in CRC metastasis through DVL2-dependent Wnt/β-catenin signaling activation

Gastroenterology Report 2023年第1期11卷 350-364页

作者： Yiting Liu Qianling Gao Xingzhi Feng Guanxing Chen Xuefei Jiang Daici Chen Zihuan Yang Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesGuangzhouGuangdongP.R.China Department of General Surgery(Colorectal Surgery) The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Artificial Intelligence Medical Research Center School of Intelligent Systems EngineeringSun Yat-sen UniversityShenzhenGuangdongP.R.China Department of Clinical Laboratory The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:aquaporin 9(AQP9)is permeable to water or other small molecules,and plays an important role in various *** previously found that AQP9 was related to the efficacy of chemotherapy in patients with colorectal cancer(CRC).This study aimed to identify the role and regulatory mechanism of AQP9 in CRC ***:The clinical significance of AQP9 was analysed by using bioinformatics and tissue *** sequencing,Dual-Luciferase Reporter Assay,Biacore,and co-immunoprecipitation were employed to demonstrate the regulatory mechanism of AQP9 in *** relationship between AQP9 and CRC metastasis was verified in vitro and in vivo by using real-time cell analysis assay,high content screening,and liver metastasis models of nude ***:We found that AQP9 was highly expressed in metastatic ***9 overexpression reduced cell roundness and enhanced cell motility in *** further showed that AQP9 interacted with Dishevelled 2(DVL2)via the C-terminal SVIM motif,resulting in DVL2 stabilization and the Wnt/b-catenin pathway ***,we identified the E3 ligase neural precursor cell expressed developmentally downregulated 4-like(NEDD4L)as a modulator regulating the ubiquitination and degradation of ***:Collectively,our study revealed the important role of AQP9 in regulating DVL2 stabilization and Wnt/β-catenin signaling to promote CRC *** the NEDD4L–AQP9–DVL2 axis might have therapeutic usefulness in metastatic CRC treatment.

关键词： aquaporin 9 colorectal cancer metastasis Dishevelled 2 Wnt/b-catenin signaling

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Up regulation of aquaporin 1,4 and 9 expressions in brain edema after rat traumatic brain injury

Up regulation of aquaporin 1,4 and 9 expressions in brain ed...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： F.YUAN,L.ZHANG,Y.CUI,L.X.XU Beijing Neurosurgical Institute,Beijing 100050,China

＜正＞Objective aquaporins（AQPs） are a family of water-selective channels that provide a major pathway for osmotically driven water transport through cell *** AQP subtypes cloned in mammalian,only AQP 1,4 and 9 were identified in the *** evidence suggests that brain AQPs play important roles for the dynamic regulation of brain water homeostasis and may be correlated with edema formation of the *** purpose of this work is to study the expression of AQP 1,4 and 9 in rat brain and their roles in brain edema after traumatic brain injury（TBI）. Methods The impact-acceleration head injury model of rat was *** rats were divided into control group and TBI groups randomly,and examined at interval times of 1,6,24 h and 7days after TBI respectively（n = 6）.Change of brain water content was assessed by brain wet / dry *** 1,4 and 9 expressions were determined using immunohistochemical staining and were semiquantified as an intensity of staining or numbers of positive staining *** immunostaining was used to assess blood-brain barrier（BBB） *** The brain water content after TBI increased at 6 *** peak at 24 h and returned to normal at 7 *** of IgG began to increase at 1 h and peaked at 6 ***, up expressions of AQP 4 were found both in astrocyte end-feet and cell bodies after *** there were positive cells immunostained with AQP 1 and 9 in edema *** most remarkable changes of the immunostaining of AQP 1,4 and 9 were occurred at 24 h after TBI,which was parallel to brain water content increases but delayed to BBB disturbance. Conclusion The good correlation between alterations in brain water content and AQP 1,4 and 9 immunostaining suggests that changes of these AQPs are involved in the development of brain *** modulation of AQP 1,4 and 9 function may provide a novel therapeutic strategy for the treatment of TBI.

关键词： traumatic brain injury brain edema aquaporin I aquaporin 4 aquaporin 9

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Auphen and dibutyryl cAMP suppress growth of hepatocellular carcinoma by regulating expression of aquaporins 3 and 9 in vivo

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World Journal of Gastroenterology 2016年第12期22卷 3341-3354页

作者： Rui Peng Guang-Xi Zhao Jing Li Yu Zhang Xi-Zhong Shen Ji-Yao Wang Jian-Yong Sun Department of Gastroenterology Zhongshan Hospital Fudan University

AIM: To investigate whether the regulation of aquaporin 3 (AQP3) and AQP9 induced by Auphen and dibutyryl cAMP (dbcAMP) inhibits hepatic ***: Expression of AQP3 and AQP9 was detected by Western blot, immunohistochemistry (IHC), and RT-PCR in HCC samples and paired non-cancerous liver tissue samples from 30 hepatocellular carcinoma (HCC) patients. A xenograft tumor model was used in vivo. Nine nude mice were divided into control, Auphen-treated, and dbcAMP-treated groups (n = 3 for each group). AQP3 and AQP9 protein expression after induction of xenograft tumors was detected by IHC and mRNA by RT-PCR analysis. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and histological evaluation were used to detect apoptosis of tumor cells, and the concentration of serum α-fetoprotein (AFP) was measured using RT-PCR and an ELISA ***: The volumes and weights of tumors decreased significantly in the Auphen- and dbcAMP-treated mice compared with the control mice (P 9 were significantly higher in thedbcAMP treatment mice than in the control mice (P 9 by dbcAMP in nude mice suppressed tumor growth of HCC, which resulted in reduced AFP levels in serum and tissues, and apoptosis of tumor cells in the Auphen- and dbcAMP-treated mice, when compared with control mice (P 9 decreased. By correlating clinicopathological and expression levels, we demonstrated that the expression of AQP3 and AQP9 was correlated with clinical progression of HCC and disease ***: AQP3 increases in HCC while AQP9 decreases. Regulation of AQP3 and AQP9 expression by Auphen and dbcAMP inhibits the development and growth of HCC.

关键词： Hepatocellular carcinoma Nude mice Auphen Dibutyryl cAMP aquaporin 3 Xenograft tumor model aquaporin 9

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Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury

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Neural Regeneration Research 2014年第24期9卷 2182-2188页

作者： Yang Wang Shuquan Zhang Min Luo Yajun Li Department of Orthopedics China-Japan Union Hospital Jilin University Department of Orthopedics Nankai Hospital School of Mathematics Jilin University

Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury.

关键词： nerve regeneration spinal cord injury hyperbaric oxygen motor function rats microenvironment aquaporin 4 aquaporin 9 neural regeneration

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