Zhou-wei Xu

Bio: Zhou-wei Xu is an academic researcher from Anhui Medical University. The author has contributed to research in topics: Angiotensin II & Receptor. The author has an hindex of 3, co-authored 5 publications receiving 25 citations.

The influence of TNF-α and Ang II on the proliferation, migration and invasion of HepG2 cells by regulating the expression of GRK2.

Abstract: Hepatocellular carcinoma (HCC) is a common digestive system malignancy that is associated with a poor prognosis. This study researched the interaction of tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II) in HCC cells proliferation, migration and invasion and examined their influence on the expression of G protein-coupled receptor kinase 2 (GRK2) and relevant receptors. Cell Counting Kit-8 and Transwell assays were performed to evaluate the effects of TNF-α and Ang II on HepG2 cells proliferation, migration and invasion. Flow cytometry was used to investigate the expression of tumor necrosis factor receptor 1 (TNFR1), angiotensin II type 1 (AT1R) and type 2 receptors (AT2R) on the surface of HepG2 cells. Additionally, Western blot was performed to assess the modulation of GRK2 expression by TNF-α and Ang II in HepG2 cells. Meanwhile, GRK2 siRNA-transfected HepG2 cells were used to confirm the effects of GRK2, TNF-α and Ang II on the proliferation, migration and invasion of GRK2-knockdown HCC cells. Finally, the expression of TNF-α, Ang II, TNFR1, AT1R, AT2R and GRK2 proteins in HCC, tumor-adjacent and normal liver tissues were tested by immunohistochemistry. The data demonstrated that TNF-α and Ang II can enhance the proliferation, migration and invasion of HepG2 cells through suppressing GRK2 expression but that the two reagents combined did not have synergistic effects. Moreover,overexpression of TNFR1 and AT1R perhaps promoted the formation and progression of HCC, while high AT2R expression had the opposite effect. This study provides new ideas for the prevention and treatment of HCC by researching the interaction and probable mechanism of different bioactive factors associated with HCC.

CP-25 exerts therapeutic effects in mice with dextran sodium sulfate-induced colitis by inhibiting GRK2 translocation to downregulate the TLR4-NF-κB-NLRP3 inflammasome signaling pathway in macrophages.

Abstract: Deficiency of G protein-coupled receptor kinase 2 (GRK2) was found to protect mice from dextran sulfate sodium (DSS)-induced colitis. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has been shown to exert anti-inflammatory immune regulatory effects in animal models of inflammatory autoimmune disease. This study aimed to investigate the of GRK2 in the pathogenesis of ulcerative colitis (UC) and its effects on macrophage polarization, macrophage subtype regulation of intestinal barrier function, and therapeutic effects of CP-25 in mice with DSS-induced colitis. We found imbalanced macrophage polarization, intestinal barrier dysfunction, and abnormal activation of GRK2 and TLR4-NF-κB-NLRP3 inflammasome signaling pathway in the colonic mucosa of patients with UC. CP-25, restored the damaged intestinal barrier function by inhibiting the transmembrane region of GRK2 in macrophages stimulated by lipopolysaccharides. CP-25 exerted therapeutic effects by ameliorating clinical manifestation, regulating macrophage polarization, and restoring abnormally activated TLR4-NF-κB-NLRP3 inflammasome signaling pathway by inhibiting GRK2. These data suggest the pathogenesis of UC may be related to the imbalance of macrophage polarization, which leads to abnormal activation of TLR4-NF-κB-NLRP3 inflammasome signaling pathway mediated by GRK2 and destruction of the intestinal mucosal barrier. CP-25 confers therapeutic effects on colitis by inhibiting GRK2 translocation to induce the downregulation of TLR4-NF-κB-NLRP3 inflammasome signaling in macrophages.

2K1C-activated Angiotensin II (Ang II) exacerbates vascular damage in a rat model of arthritis through the ATR/ERK1/2 signaling pathway

Abstract: To explore the role and mechanism of the two-kidney one-clip (2K1C)-activated Angiotensin II (Ang II) in the development of vascular damage in adjuvant-induced arthritis (AA) rats. 2K1C rats were established in normal and AA rats for 35 days. Hypertension, endothelial dysfunction, and vascular hypertrophy induced by 2K1C-activated Ang II in systemic inflammation rats were evaluated. The levels of Ang II and TNF-α in serum were observed by ELISA kits. Expressions of Ang II/ATR/ERK1/2 signaling pathway molecules in the aorta were tested by immunohistochemistry or western blot. The migration and capillary tube formation abilities of human umbilical vein endothelial cells (HUVECs) were tested by migration chamber and capillary tube formation assays. The level of Ang II in serum was significantly increased in 2K1C rats. Compared with AA rats, the high level of Ang II activated by 2K1C reduced the endothelium-dependent vasodilator responses to acetylcholine (ACh) in the thoracic aorta and exacerbated endothelial dysfunction and vascular hypertrophy. Expressions of ATR, GRK2, p-ERK1/2, and p-NF-κB were significantly increased in the aorta of AA combined with 2K1C rats. The migration and capillary tube formation abilities of HUVECs were significantly enhanced by Ang II and TNF-α co-stimulations in vitro through the ATR/ERK1/2 signaling pathway compared to those stimulated with TNF-α. 2K1C-activated Ang II is involved in aggravated vascular injury and endothelial dysfunction through the ATR/ERK1/2 signaling pathway in AA rats.

Effect of PLC-β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma.

Abstract: OBJECTIVE To study the roles of AT1R, PLC-β1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation. METHODS ELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver tissue of HCC patients, and the correlation between AT1R, PLC-β1 and CaM and postoperative survival status of patients was followed up and determined. CCK-8 method was used to screen the doses of Ang II and candesartan sensitive to HepG2 and HCCLM3 cells. Transwell experiment was used to observe the effects of different drugs on the migration and invasion activity of HCC cells. Meanwhile, flow cytometry and Western blot were used to detect the expression levels of AT1R, PLC-β1 and CaM in the cells. Then PLC-β1 siRNA was selected to transfect HCC cells, so as to further clarify the mechanism of the above signal proteins. HepG2 cells were inoculated under the hepatic capsule of mice to induce the formation of HCC in situ. Ang II and candesartan were used to stimulate HCC mice to observe the difference in liver appearance and measure the liver index. Finally, ELISA and immunofluorescence experiments were selected to analyze the levels of target proteins in mouse serum and liver tissue. RESULTS The expression levels of target proteins in serum and liver tissue of HCC patients were significantly increased, and the postoperative survival time of patients with high expression of AT1R, PLC-β1 or CaM was obviously shortened. Ang II and candesartan could significantly promote and inhibit the motility of HCC cells, and had different effects on the levels of AT1R, PLC-β1 and CaM in cells. However, in hepatocellular carcinoma cells transfected with PLC-β1 siRNA, the intervention ability of drugs was obviously weakened. Ang II could significantly promote the formation and progression of mouse HCC, while candesartan had the opposite effect. Meanwhile, medications could affect the expressions of target proteins in mouse serum and liver tissue. CONCLUSION AT1R, PLC-β1 and CaM may be risk factors affecting the formation and prognosis of HCC, and the PLC-β1/CaM signaling pathway mediated by AT1R is an important way to regulate the migration and invasion activity of HCC cells.

Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity

Abstract: Background: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. Objective: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity …

Новые данные о связи ревматоидного артрита и атеросклероза (An update on the relationships between rheumatoid arthritis and atherosclerosis)

Abstract: Ревматоидный артрит (РА) является хрониче-ским системным воспалительным заболеванием, характеризующимся суставными и внесуставными проявлениями. Среди пациентов РА сердечно-сосудистые заболевания (ССЗ) является самой важной причиной смертности и увеличения за-болеваемости [1]. Несколько исследований пред-положили, что риск развития атеросклероза, как основной причины ССЗ, увеличивается и при РА. Причина прогрессирования атеросклероза при РА неясна, и увеличение риска развития ССЗ не мо-жет быть полностью объяснено традиционными факторами риска, такими как возраст, пол, куре-ние, артериальная гипертония или сахарный диа-бет 2 типа (СД2) [2]. Клинические, лабораторные и эпидемиологические исследования показали, что прогрессирующее системное воспаление – один из нетрадиционных факторов увеличения сердечно-сосудистого риска у этих пациентов [3].Ранее, атеросклероз считался следствием пас-сивного накопления липидов в стенке сосуда, но, в настоящее время признано, что это динамический воспалительный процесс, начинающийся с актива-ции сосудистого эндотелия, миграции лейкоцитов, окисления липидов и достигающий высшей точки при дестабилизации атеросклеротической бляшки и тромбозе [4]. РА является примером хроническо-го системного воспалительного заболевания и, что интересно, поразительные общие черты были от-мечены между патогенезом атеросклероза и РА [5]. Известно, что хроническое системное воспаление в популяции в целом и у пациентов с РА приводит к учащению сердечно-сосудистых событий (ССС) помимо традиционных факторов риска.Увеличенный риск ССЗ у пациентов с РА недавно стал объектом интенсивных исследований. Буду-щие исследования необходимы, чтобы объяснить, как системное воспаление приводит к развитию атеросклероза, и это может помочь развитию но-вых терапевтических направлений, которые в со-стоянии уменьшать риск ССЗ при РА.1. Синовиальное и сосудистое воспалениеАтеросклеротическая бляшка и воспаленная си-новиальная оболочка имеют общие черты, связан-ные с накоплением воспалительных макрофагов, моноцитов и Т-клеток. РА и атеросклероз можно разделить по системному и локальному принципу активации воспалительного процесса: с активацией T-клеток, активацией продукции фактора некроза опухоли-α (ФНО-α) и интерлeйкина 6 (IL-6), уве-личением экстрацелюлярных матричных металло-протеаз и экспрессией молекул адгезии лейкоци-тов. Кроме того, и РА и атеросклероз тесно связаны с повышенной регуляцией Th1-зависимого иммун-ного ответа [4, 5].Самое частое место развития воспаления при РА – синовиальная оболочка, но провоспалитель-ные цитокины, такие как TNF-α и IL-6, оказавшие-ся в системном кровотоке оказывают и множество эффектов на отдаленные органы, включая печень, жировую ткань, скелетную мускулатуру, иммунную систему и эндотелий [6]. В результате системное

Small interfering RNA-mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is one of the lethal and difficult-to-cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence-specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA-mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti-HCC agents is the subject of the current review. siRNA-based gene therapies could be one of the main feasible approaches for HCC therapy in the future.

Cathepsin C Interacts with TNF-α/p38 MAPK Signaling Pathway to Promote Proliferation and Metastasis in Hepatocellular Carcinoma

Abstract: Purpose Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC. Materials and methods HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools. Results By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p Conclusion Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.