个人简介

Ph.D. (Doctor of Philosophy) M.Sc. (Master of Science)

研究领域

Molecular Biology and Disease

Vascular Smooth Muscle and Human Diseases Proliferation of vascular smooth muscle cells (SMCs) is a key event in the development of atherosclerosis, which has been known for many years. However, the exact mechanisms remain to be addressed. In this project, we are trying to understand whether and how mature SMCs contribute to this proliferative vascular disease, and if other non-mature muscle cells within the blood vessel wall also contribute to the development of the lesions. It is also our interest to investigate how proliferative SMCs develop into foam cells containing excessive cholesterols in atherosclerotic lesions. The ultimate goal is to define cellular and molecular targets for the development of therapeutic approaches. Early studies revealed similarities between SMC proliferation in the blood vessel with that in human uterine leiomyoma, a benign smooth muscle tumor. Therefore, we are also interested in understanding why myometrial SMCs undergo abnormal proliferation. At the molecular level, we have been focusing on several compounds and proteins as listed below. Tuberin Tuberin is the gene product of tuberous sclerosis complex (TSC)-2 and has GTPase activating protein (GAP) functions. Malfunction of tuberin due to either mutation or deficiency results in a condition called tuberous sclerosis complex, a rare multi-system genetic disease, which is accompanied by proliferation of vascular SMCs in renal angioleiomyomas. Therefore, we are trying to understand how tuberin is involved in the regulation of smooth muscle functions including the cell cycle. Phospholipase D (PLD) In response to various stimuli, PLD hydrolyzes the phosphodiester bond of the glycerolipid phosphatidylcholine to generate phosphatidic acid and free choline, which likely regulate the cell cycle. We are interested in how PLD activation stimulates proliferation and migration of vascular SMCs. Myocardin As a co-transcriptional factor of serum response factor, myocardin specifically stimulates the expression of smooth muscle contractile proteins. Our recent studies have revealed inhibitory effects of myocardin on the cell cycle. We are interested in understanding how myocardin directs the differentiation of stem cells. Uridine adenosine tetraphosphate (Up4A) Up4A is a novel endothelium-derived contraction factor that potently stimulates proliferation of human vascular SMCs. The plasma concentration of Up4A is significantly elevated in juvenile hypertensive patients. We are interested in further understanding its roles in the pathogenesis of hypertension and atherosclerosis. 2-Methoxyestradiol (2-ME) 2-ME is an estrogen metabolite with significant effects on the smooth muscle cell cycle. It causes mitotic apoptosis of human vascular SMCs. Our recent studies revealed its inhibitory effect on the development of hypertension in rats. We wish to understand more about the mechanism behind this effect and hope to develop analogs for specific clinical diseases.

近期论文

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Tan X, Gao J, Shi Z, Tai S, Chan LL, Yang Y, Peng DQ, Liao DF, Jiang ZS, Chang Y, Gui Y, Zheng XL. MG132 Induces Expression of Monocyte Chemotactic Protein- Induced Protein 1 in Vascular Smooth Muscle Cells. J Cell Physiol. 2016 Mar 31. [Epub ahead of print] Pubmed Tai S, Hu XQ, Peng DQ, Zhou SH, Zheng XL. The roles of autophagy in vascular smooth muscle cells. Int J Cardiol. 2016;211: 1-6. Pubmed Zhou YX, Shi Z, Singh P, Yin H, Yu YN, Li L, Walsh MP, Gui Y, Zheng XL. Potential Role of Glycogen Synthase Kinase-3β in Regulation of Myocardin Activity in Human Vascular Smooth Muscle Cells. J Cell Physiol. 2016;231: 393-402. Pubmed Klionsky DJ ... Zheng XL, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1): 1-222. Pubmed Xie W, Li L, Zhang M, Cheng HP, Gong D, Lv YC, Yao F, He PP, Ouyang XP, Lan G, Liu D, Zhao ZW, Tan YL, Zheng XL, Yin WD, Tang CK. MicroRNA-27 Prevents Atherosclerosis by Suppressing Lipoprotein Lipase-Induced Lipid Accumulation and Inflammatory Response in Apolipoprotein E Knockout Mice. PLoS One. 2016;11(6): e0157085. Pubmed Yao Y, Zhang X, Chen HP, Li L, Xie W, Lan G, Zhao ZW, Zheng XL, Wang ZB, Tang CK. MicroRNA-186 promotes macrophage lipid accumulation and secretion of pro-inflammatory cytokines by targeting cystathionine γ-lyase in THP-1 macrophages. Atherosclerosis. 2016;250: 122-132.Pubmed Gu HF, Li HZ, Tang YL, Tang XQ, Zheng XL, Liao DF. Nicotinate-Curcumin Impedes Foam Cell Formation from THP-1 Cells through Restoring Autophagy Flux. PLoS One. 2016;11(4): e0154820.Pubmed Zhang M, Li L, Xie W, Wu JF, Yao F, Tan YL, Xia XD, Liu XY, Liu D, Lan G, Zeng MY, Gong D, Cheng HP, Huang C, Zhao ZW, Zheng XL, Tang CK. Apolipoprotein A-1 binding protein promotes macrophage cholesterol efflux by facilitating apolipoprotein A-1 binding to ABCA1 and preventing ABCA1 degradation. Atherosclerosis. 2016;248: 149-159. Pubmed Qin L, Zhu N, Ao BX, Liu C, Shi YN, Du K, Chen JX, Zheng XL, Liao DF. Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis. Int J Mol Sci. 2016 Mar 22;17(3). Review. Pubmed Lan G, Xie W, Li L, Zhang M, Liu D, Tan YL, Cheng HP, Gong D, Huang C, Zheng XL, Yin WD, Tang CK. MicroRNA-134 Actives lipoprotein lipase-mediated Lipid Accumulation and Inflammatory Response by Targeting Angiopoietin-Like 4 in THP-1 Macrophages. Biochem Biophys Res Commun. 2016;472(3): 410–417. Pubmed Liu D, Zhang M, Xie W, Lan G, Cheng HP, Gong D, Huang C, Lv YC, Yao F, Tan YL, Li L, Zheng XL, Tang CK. MiR-486 Regulates Cholesterol Efflux by Targeting HAT1. Biochem Biophys Res Commun. 2016;472(3): 418-424. Pubmed Peng L, Zhang Z, Zhang M, Yu X, Yao F, Tan Y, Liu D, Gong D, Chong H, Liu X, Zheng XL, Tian G, Tang C. Macrophage-activating lipopeptide-2 downregulates the expression of ATP-binding cassette transporter A1 by activating the TLR2/NF-кB/ZNF202 pathway in THP-1 macrophages.Acta Biochim Biophys Sin (Shanghai). 2016; 48 (4): 363-370. Pubmed Gong D, Che HP, Xie W, Zhang M, Liu D, Lan G, Huang C, Zhao ZW, Chen LY, Yao F, Tan YL, Li L, Xia XD, Zheng XL, Wang ZB, Tang CK. Cystathionine γ-Lyase(CSE)/Hydrogen Sulfide System Is Regulated by miR-216a and Influences Cholesterol Efflux in Macrophages via the PI3K/AKT/ABCA1 pathway. Biochem Biophys Res Commun. 2016;470(1): 107-16. Pubmed Qin L, Yang YB, Yang YX, Zhu N, Liu Z, Ni YG, Li SX, Zheng XL, Liao DF. Inhibition of Macrophage-Derived Foam Cell Formation by Ezetimibe via the Caveolin-1/MAPK Pathway. Clin Exp Pharmacol Physiol. 2016;43(2): 182-92. Pubmed Li L, Xie W, Zheng XL, Yin WD, Tang CK. A novel peptide adropin in cardiovascular diseases. Clin Chim Acta. 2016;453: 107-113. Pubmed Gui Y, Shi Z, Wang ZY, Li JJ, Xu C, Tian RJ, Song XX, Walsh MP, Li D, Gao J, Zheng XL. The GPER agonist G-1 induces mitotic arrest and apoptosis in human vascular smooth muscle cells independent of GPER. J Cell Physiol. 2015;230: 885-95 Pubmed He PP, OuYang XP, Li Y, Lv YC, Wang ZB, Yao F, Xie W, Tan YL, Li L, Zhang M, Lan G, Gong D, Cheng HP, Zhong HJ, Liu D, Huang C, Li ZX, Zheng XL, Yin WD, Tang CK. MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout Mice. PLoS One. 2015;10(9): e0138788 Pubmed Peng J, Lv YC, He PP, Tang YY, Xie W, Liu XY, Li Y, Lan G, Zhang M, Zhang C, Shi JF, Zheng XL, Yin WD, Tang CK. Betulinic Acid Downregulates Expression of Oxidative Stress-Induced Lipoprotein Lipase via the PKC/ERK/c-Fos Pathway in RAW264.7 Macrophages. Biochimie. 2015; 119: 192-203. [Epub ahead of print] Pubmed Yu XH, Zheng XL, Tang CK. Peroxisome Proliferator-Activated Receptor α in Lipid Metabolism and Atherosclerosis. Adv Clin Chem. 2015;71: 171-203 Pubmed Yao F, Lv YC, Zhang M, Xie W, Tan YL, Gong D, Cheng HP, Liu D, Li L, Liu XY, Zheng XL, Tang CK. Apelin-13 Impedes Foam Cell Formation by Activating Class III PI3K/Beclin-1-Mediated Autophagic Pathway. Biochem Biophys Res Commun. 2015;466: 637-43 Pubmed