mTOR; Inflammation ; Macrophage ; Arginase-II ; Obesity; Vascular Dysfunction
Huang Ji, Liang Xiujie, Ladeiras Diogo, Fellay Benoit, Ming Xiu-Fen, Yang Zhihong (2021), Role of tubular epithelial arginase-II in renal inflammaging, in npj Aging and Mechanisms of Disease
, 7(1), 5-5.
Huang Ji, Ladeiras Diogo, Yu Yi, Ming Xiu-Fen, Yang Zhihong (2021), Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney, in Frontiers in Pharmacology
, 11, 1-13.
Yu Yi, Ladeiras Diogo, Xiong Yuyan, Boligan Kayluz Frias, Liang Xiujie, Gunten Stephan, Hunger Robert E., Ming Xiu‐Fen, Yang Zhihong (2020), Arginase‐II promotes melanoma migration and adhesion through enhancing hydrogen peroxide production and STAT3 signaling, in Journal of Cellular Physiology
, 235(12), 9997-10011.
Huang Ji, Liu Chang, Ming Xiu-Fen, Yang Zhihong (2020), Inhibition of p38mapk Reduces Adipose Tissue Inflammation in Aging Mediated by Arginase-II, in Pharmacology
, 105(9-10), 491-504.
Yu Yi, Xiong Yuyan, Ladeiras Diogo, Yang Zhihong, Ming Xiu-Fen (2019), Myosin 1b Regulates Nuclear AKT Activation by Preventing Localization of PTEN in the Nucleus, in iScience
, 19, 39-53.
Liang Xiujie, Arullampalam Prakash, Yang Zhihong, Ming Xiu-Fen (2019), Hypoxia Enhances Endothelial Intercellular Adhesion Molecule 1 Protein Level Through Upregulation of Arginase Type II and Mitochondrial Oxidative Stress, in Frontiers in Physiology
, 10(105), 491.
Huang Ji, Montani Jean-Pierre, Verrey François, Feraille Eric, Ming Xiu-Fen, Yang Zhihong (2018), Arginase-II negatively regulates renal aquaporin-2 and water reabsorption, in The FASEB Journal
, 32(10), 5520-5531.
Yu Yi, Xiong Yuyan, Montani Jean-Pierre, Yang Zhihong, Ming Xiu-Fen (2018), Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and apoptosis, in Cell Death & Disease
, 9(3), 313-313.
Pillai Samyuktha Muralidharan, Seebeck Petra, Fingerhut Ralph, Huang Ji, Ming Xiu‐Fen, Yang Zhihong, Verrey François (2018), Kidney Mass Reduction Leads to l ‐Arginine Metabolism‐Dependent Blood Pressure Increase in Mice, in Journal of the American Heart Association
, 7(5), e008025.
Zhu Cuicui, Yu Yi, Montani Jean-Pierre, Ming Xiu-Fen, Yang Zhihong (2017), Arginase-I enhances vascular endothelial inflammation and senescence through eNOS-uncoupling, in BMC Research Notes
, 10(1), 82-82.
Xiong Yuyan, Yepuri Gautham, Montani Jean-Pierre, Ming Xiu-Fen, Yang Zhihong (2017), Arginase-II Deficiency Extends Lifespan in Mice, in Frontiers in Physiology
, 8, 682.
Xiong Yuyan, Yepuri Gautham, Necetin Sevil, Montani Jean-Pierre, Ming Xiu-Fen, Yang Zhihong (2017), Arginase-II Promotes Tumor Necrosis Factor-α Release From Pancreatic Acinar Cells Causing β-Cell Apoptosis in Aging, in Diabetes
, 66(6), 1636-1649.
Reiner Martin F., Akhmedov Alexander, Stivala Simona, Keller Stephan, Gaul Daniel S., Bonetti Nicole R., Savarese Gianluigi, Glanzmann Martina, Zhu Cuicui, Ruf Wolfram, Yang Zhihong, Matter Christian M., Lüscher Thomas F., Camici Giovanni G., Beer Juerg H. (2017), Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression, in Cardiovascular Research
, 113(1), 61-69.
Yang Zhihong, Ming Xiu-Fen (2017), Adventitia and perivascular adipose tissue – the integral unit in vascular disease, in Magnus Bäck, Krams Robert (ed.), OXFORD University Press, OXFORD, 309.
Huang Ji, Rajapakse Angana, Xiong Yuyan, Montani Jean-Pierre, Verrey François, Ming Xiu-Fen, Yang Zhihong (2016), Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity, in Frontiers in Physiology
, 7, 560.
Liu Chang, Rajapakse Angana G., Riedo Erwin, Fellay Benoit, Bernhard Marie-Claire, Montani Jean-Pierre, Yang Zhihong, Ming Xiu-Fen (2016), Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation, in Scientific Reports
, 6(1), 20405-20405.
Yu Yi, Xiong Yuyan, Montani Jean-Pierre, Yang Zhihong, Ming Xiu-Fen (2016), En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries, in Journal of Visualized Experiments
, (108), 53718.
Klionsky Daniel J, Abdelmohsen Kotb, Abe Akihisa, Abedin Md Joynal, Abeliovich Hagai, Acevedo Arozena Abraham, Adachi Hiroaki, Adams Christopher M, Adams Peter D, Adeli Khosrow, Adhihetty Peter J, Adler Sharon G, Agam Galila, Agarwal Rajesh, Aghi Manish K, Agnello Maria, Agostinis Patrizia, Aguilar Patricia V, Aguirre-Ghiso Julio, Airoldi Edoardo M, Ait-Si-Ali Slimane, Akematsu Takahiko, Akporiaye Emmanuel T, Al-Rubeai Mohamed, et al. (2016), Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), in Autophagy
, 12(1), 1-222.
Background: Arginase, the L-arginine-ureahydrolase, metabolizes L-arginine to urea and L-ornithine. Two isoenzymes i.e., arginase-I (Arg-I) and arginase-II (Arg-II) exist. While Arg-I is mainly expressed in the liver for ammonia detoxification, Arg-II is expressed in extrahepatic cells including vascular cells and macrophages, participating in chronic inflammatory diseases, e.g., insulin resistance and atherosclerosis, which is believed to be due to L-arginine depletion for nitric oxide (NO) production. However, our recent research suggests that Arg-II promotes macrophage pro-inflammatory responses under the disease conditions independently of inducible NO-synthase in macrophages, impairs endothelial autophagy (a self-repairing mechanism), causes smooth muscle cell apoptosis/senescence through mTORC2-Akt-mTORC1-S6K1 signalling independently of its L-arginine metabolizing activity (pleiotropic function). Research aims: Given the importance of mTORC1-S6K1 in insulin resistance and the pro-inflammatory role of Arg-II in macrophage, we wish to elucidate the molecular mechanisms of the pleiotropic function of Arg-II in mTOR signaling and dissect the macrophage-specific role of Arg-II’s enzymatic activity-dependent and -independent effects in obesity-associated insulin resistance and vascular dysfunction. Scientific relevance: The final results of this project will not only elucidate molecular mechanisms of the discovered novel pleiotropic Arg-II function in activation of mTORC2-Akt-mTORC1-S6K1 signalling pathway, which is independent of its L-arginine metabolizing activity, but will also for the first time provide new insights into the specific contribution of WT and/or inactive Arg-II in macrophages to obesity-associated inflammation, insulin resistance, and vascular dysfunction. The expected results, if proved, would suggest that targeting Arg-II expression rather than enzymatic activity would be more effective to treat obesity-associated insulin resistance and vascular complications.