Modulation of the VEGF/AKT/eNOS signaling pathway to regulate liver angiogenesis to explore the anti-hepatic fibrosis mechanism of curcumol

Zheng, Yang; Wang, Jia-Ru; Zhao, Tiejian; Wang, Lei; Wang, Jiahui

doi:10.1016/j.jep.2021.114480

Cited by 24 publications

(13 citation statements)

References 28 publications

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“…In general, PI3K/Akt acts as a usual transduction molecule in fibrotic diseases, is not only related to promote the production of collagen, but also to participate in the activation of myofibroblasts ( 56 ). Recent experiments have been shown that phosphorylation level of Akt is increased in liver fibrosis, which is regarding as a signal of eNOS expression, and resulting in production of NO ( 57 ). On the contrary, the inhibition of Akt/eNOS is confirmed by liver GRK2 in STZ-induced diabetic mice ( 58 ).…”

Section: Relationship Between Grk2 and Fibrosis-associated Pathwaysmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

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Section: Relationship Between Grk2 and Fibrosis-associated Pathwaysmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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“…Hepatic fibrosis is a pathological condition characterized by excessive ECM production and inflammatory cell infiltration [25]. Cirrhosis, portal hypertension, and even liver cancer may occur from hepatic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Olmesartan Improves Hepatic Sinusoidal Remodeling in Mice with Carbon Tetrachloride-Induced Liver Fibrosis

Wang

et al. 2022

BioMed Research International

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Aim. In mice with liver fibrosis produced by carbon tetrachloride (CCl4), the effects of olmesartan on intrahepatic angiogenesis and sinusoidal remodeling will be evaluated. Methods. By injecting CCl4 into the peritoneal cavity, we established a mouse model of liver fibrosis. Using Sirius red and Masson trichrome staining, the extent of liver fibrosis in the animals was determined. Using immunohistochemical labeling and western blotting, the level of α-smooth muscle actin (α-SMA) expression, a characteristic of hepatic stellate cell activation, was assessed. Electron microscopy was used to determine the effect of olmesartan on hepatic sinusoidal capillarization, and immunohistochemical labeling was used to determine the expression levels of endothelial and basement membrane proteins in mouse liver tissues. Platelet-derived growth factor (PDGF), IL-10, vascular endothelial growth factor (VEGF), and angiotensin II levels in mouse serum were measured by Luminex multifactor analysis and ELISA. Olmesartan’s effect on the angiotensin II type 1 receptor (AT1R) and the VEGF receptor (VEGFR) was evaluated using western blotting. Results. Olmesartan reduced CCl4-induced inflammatory cell infiltration and collagen deposition to alleviate liver fibrosis. α-SMA expression was decreased, and HSC activation was inhibited in mouse liver tissues by olmesartan treatment. In addition, hepatic sinusoidal capillarization was improved under the action of olmesartan. The expression of collagen IV, fibronectin, CD31, and von Willebrand factor (VWF) in the olmesartan group was also markedly downregulated. In fibrotic mice, olmesartan medication decreased the levels of PDGF, VEGF, and angiotensin II, but it increased the level of IL-10. Moreover, olmesartan reduced the expression of VEGFR-1, VEGFR-2, and AT1R relative to CCl4-induced liver fibrosis. Conclusions. In mice with CCl4-induced fibrosis, olmesartan lowers angiogenesis and improves hepatic sinusoidal remodeling, according to our findings. By acting on the angiotensin II-AT1R-VEGF axis, this is achieved.

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Section: Ctrp6 In Hepatocellular Carcinomamentioning

confidence: 94%

“…Inhibition of Akt phosphorylation decreased angiogenesis of HCC ( Xie et al, 2021 ). Additionally, hepatic angiogenesis can be regulated by VEGF/Akt/eNOS signaling pathway ( Zheng et al, 2021 ). Moreover, pretreatment of Hep3B cells with insulin-like growth factor 1 (IGF-1), an activator of Akt, could restore the changes in cell biological behavior by CTRP6-siRNA transfection.…”

Section: Ctrp6 In Hepatocellular Carcinomamentioning

confidence: 99%

Advances in the functions of CTRP6 in the development and progression of the malignancy

Qian²,

Qian³

et al. 2022

Front. Genet.

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CTRP6, a member of the C1q/TNF-related protein (CTRP) family, has gained increasing scientific interest because of its regulatory role in tumor progression. Previous studies have shown that CTRP6 is closely involved in regulating various pathophysiological processes, including glucose and lipid metabolism, cell proliferation, apoptosis, and inflammation. To date, CTRP6 has been identified as related to eight different malignancies, including lung cancer, oral cancer, gastric cancer, colon cancer, liver cancer, bladder cancer, renal cancer, and ovarian cancer. CTRP6 is reported to be associated with tumor progression by activating a series of related signal networks. This review article mainly discusses the biochemistry and pleiotropic pathophysiological functions of CTRP6 as a new molecular mediator in carcinogenesis, hoping that the information summarized herein could make a modest contribution to the development of novel cancer treatments in the future.

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Modulation of the VEGF/AKT/eNOS signaling pathway to regulate liver angiogenesis to explore the anti-hepatic fibrosis mechanism of curcumol

Cited by 24 publications

References 28 publications

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Olmesartan Improves Hepatic Sinusoidal Remodeling in Mice with Carbon Tetrachloride-Induced Liver Fibrosis

Advances in the functions of CTRP6 in the development and progression of the malignancy

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