JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Yi Zhao,Zi-Yan Hu,Ming Lou,Fu-Wei Jiang,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Shuo Liu,Yu-Sheng Shi,Hong-Mei Zhu,Jin-Long Li
Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.
研究领域:
毒理学
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胃肠病学
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分子生物学
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高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-15
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IF 14.7
Yao Mingyu,Zeng Zhenhai,Li Siheng,Zou Zhilin,Chen Zhongxing,Chen Xinyi,Gao Qingyi,Zhao Guoli,Chen Aodong,Li Zheng,Wang Yiran,Ning Rui,McAlinden Colm,Zhou Xingtao,Huang Jinhai
Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2 , as well as aquaporin 1 and β2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2 , or aquaporin 1 and β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.
研究领域:
分子生物学
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遗传学
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眼科学
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神经科学
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PubMed
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Lili Fan,Shukun Qu,Chenxue Miao,Dongjie Wu,Yuan Rao,Weisong Xu,Yanping He,Guang Song
Oxidative stress is a key pathological factor that contributes to blood–brain barrier (BBB) disruption during ischemic injury. Panax notoginseng saponins (PNS), the primary bioactive components of Panax notoginseng , possess potent antioxidative and vasoprotective activities. This study aimed to elucidate the molecular mechanisms by which PNS regulate endothelial integrity and BBB permeability under oxidative stress conditions. Mouse brain microvascular endothelial cells (bEnd.3) were treated with hydrogen peroxide to induce oxidative damage, followed by intervention with PNS. Transcriptomic and proteomic analyses revealed that Akap12 (A-kinase anchoring protein 12) and Aquaporin 1 (AQP1) were key molecules involved in PNS-mediated endothelial protection. H₂O₂ exposure markedly suppressed Akap12 expression and inhibited the PI3K/AKT signaling pathway, leading to elevated AQP1 expression and increased BBB permeability. PNS treatment reversed these effects by restoring Akap12 expression, reactivating PI3K/AKT signaling, and reducing AQP1 levels. Functional validation further showed that AQP1 dysregulation altered the expression balance of tight junction proteins, including Claudin-5 and ZO-1, thereby impairing barrier function. Collectively, these findings demonstrate that PNS protect endothelial cells from oxidative injury by activating Akap12-dependent PI3K/AKT signaling and modulating AQP1-associated tight junction remodeling. This study provides new mechanistic insights into the molecular basis of PNS-mediated BBB protection and suggests potential therapeutic targets for oxidative or ischemic cerebrovascular diseases.
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Scientific Reports
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2026
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IF 4.9
Qian Jingyu,Tang Xiaoyun,Ye Longji,Jin Panpan,Qin Zhongqiang,Wang Rongxin,Guo Hongyan,Li Miao
The development of hepatocellular carcinoma may be regulated by exosome-mediated cell-cell communication. GPC1-enriched exosomes have been associated with malignant phenotypes, while AQP1 has been related to tumor development and metastasis. The functional association of AQP1 and exosomal GPC1 in vivo remains to be clarified. Co-immunoprecipitation was applied to test the interaction of AQP1 with exosomal GPC1 in HCC cells. We generated a mouse xenograft model using control cells and AQP1 knockdown cells, with or without treatment with GPC1-high exosomes. Tumor growth was monitored by longitudinal caliper measurements and endpoint tumor weight. Histology and molecular characteristics were profiled using H&E staining, immunofluorescence, and immunohistochemistry. The proteins associated with ERK and MEK signaling pathways were detected through western blotting. Co-immunoprecipitation of AQP1 and GPC1 demonstrated a recovery of AQP1 and exosomal GPC1 in the same protein complex. AQP1 knockdown was accompanied by reduced xenograft tumor growth, and diminished tumor-promoting effect of GPC1-high exosomes. Tissue examinations revealed coordinated alterations in marker expression and proliferative state in all treatment groups. Total ERK and total MEK were largely similar across groups; phospho-ERK and phospho-MEK display condition-specific differences. Tumor AQP1 staining was markedly greater than that of peritumoral tissue. These data suggest that the AQP1 status may influence tumor sensitivity to GPC1 enriched exosomal stimulation in vivo, and suggest that further analysis of AQP1 as an effector in exosome related oncogenic activity in HCC is warranted.
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HEARING RESEARCH
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2024
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IF 2.5
Huilin Lao,Yafeng Zhu,Mei Yang,Lingshuo Wang,Jie Tang,Hao Xiong
Hair cells in the cochlear sensory epithelia serve as mechanosensory receptors, converting sound into neuronal signals. The basal sensory epithelia are responsible for transducing high-frequency sounds, while the apex handles low-frequency sounds. Age-related hearing loss predominantly affects hearing at high frequencies and is indicative of damage to the basal sensory epithelia. However, the precise mechanism underlying this site-selective injury remains unclear. In this study, we employed a microscale proteomics approach to examine and compare protein expression in different regions of the cochlear sensory epithelia (upper half and lower half) in 1.5-month-old (normal hearing) and 6-month-old (severe high-frequency hearing loss without hair cell loss) C57BL/6J mice. A total of 2,386 proteins were detected, and no significant differences in protein expression were detected in the upper half of the cochlear sensory epithelia between the two age groups. The expression of 20 proteins in the lower half of the cochlear sensory epithelia significantly differed between the two age groups (e.g., MATN1, MATN4, and AQP1). Moreover, there were 311 and 226 differentially expressed proteins between the upper and lower halves of the cochlear sensory epithelia in 1.5-month-old and 6-month-old mice, respectively. The expression levels of selected proteins were validated by Western blotting. These findings suggest that the spatial differences in protein expression within the cochlear sensory epithelia may play a role in determining the susceptibility of cells at different sites of the cochlea to age-related damage.
研究领域:
分子生物学
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蛋白质组学
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听力科学
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衰老研究
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高影响因子
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