EXPRESSION OF ANTI-ANGIOGENIC GENES IN SUBCUTANEOUS ADIPOSE TISSUE OF THE OBESE INDIVIDUALS WITH PRE-DIABETES AND TYPE 2 DIABETES
DOI: http://dx.doi.org/10.30970/sbi.0602.226
Abstract
Accumulating evidence raises the hypothesis that dysregulation of different intrinsic mechanisms which control most metabolic processes are involved in the development of obesity, metabolic syndrome and type 2 diabetes mellitus, the most profound public health problems. Angiogenesis is an important component of different proliferative processes, in particular, fat tissue growth. Moreover, dysregulation of molecular components of the angiogenesis system can contributes to the development of diabetic complications. We have studied the expression levels of genes related to regulation of angiogenesis (TIMP1, TIMP2, TIMP3, TIMP4, THBS1, THBS2, THBS3, ADAMTS5, LUM, DCN, IL6 and ZEB1) in subcutaneous adipose tissue of obese individuals as well as obese patients with impaired glucose tolerance (prediabetic) and type 2 diabetes using real-time quantitative PCR. We have shown that the expression level of most of these genes with anti-angiogenic properties significantly increases in subcutaneous adipose tissue of obese individuals versus lean patients, being more intense for TIMP1, TIMP2, THBS2 and LUM genes. Increased expression level of TIMP1, TIMP2, TIMP3, ADAMTS5 as well as THBS1 and THBS2 in adipose tissue was found in obese patients with impaired glucose tolerance. At the same time, expression of genes which encode for TIMP1 and TIMP2 strongly decreased in adipose tissue of obese individuals with type 2 diabetes versus subjects with glucose intolerance. Results of this study provide strong evidence that expression of genes mostly related to suppression of angiogenesis is dysregulated in adipose tissue of obese individuals as well as in obese patients with glucose intolerance and type 2 diabetes. It is possible that these changes in the expression of TIMP and THBS genes in adipose tissue in obesity as well as in obese individuals with impaired glucose tolerance and type 2 diabetes can contribute to fat tissue storage, insulin resistance and the development of diabetic complications.
Keywords
Full Text:
PDFReferences
1. Bray M.S., Young M.E. The role of cell-specific circadian clocks in metabolism and disease. Obesity Reviews, 2009; 10(Suppl. 2): 6-13. | |
| |
2. Bray M.S., Young M.E. Regulation of Fatty Acid Metabolism by Cell Autonomous Circadian Clocks: Time to Fatten up on Information? The Journal of Biological Chemistry, 2011; 286(14): 11883-11889. | |
| |
3. Turek F.W., Joshu C., Kohsaka A. et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science, 2005; 308(5724): 1043-1045. | |
| |
4. Kovac J., Husse J., Oster H. A time to fast, a time to feast: the crosstalk between metabolism and the circadian clock. Molecules and Cells, 2009; 282(2): 75-80. | |
| |
5. Scott E.M.,Carter A.M.,Grant P.J. Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in manClock polymorphisms and obesity. International Journal of Obesity, 2008; 32(4): 658-662. | |
| |
6. Ando H., Kumazaki M., Motosugi Y. et al. Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice. Endocrinology, 2011; 152(4): 1347-1354. | |
| |
7. Takahashi K., Mernaugh R.L., Friedman D.B. et al. Thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase. The Proceeding of the National Academy of Sciences of the United States of America, 2012; 109(6): 1985-1990. | |
| |
8. Neill T., Painter H., Buraschi S. et al. Decorin antagonizes the angiogenic network: concurrent inhibition of Met, hypoxia inducible factor 1alpha, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3. The Journal of Biological Chemistry, 2012; 287(8), 5492-5506. | |
| |
9. Zhao,C.Q., Zhang,Y.H., Jiang,S.D. et al. ADAMTS-5 and intervertebral disc degeneration: the results of tissue immunohistochemistry and in vitro cell culture. Journal of Orthopedy Research, 2011; 29(5): 718-725. | |
| |
10. MacLauchlan S., Yu J., Parrish M. et al. Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2. The Proceeding of the National Academy of Sciences of the United States of America, 2011; 108(46): E1137-E1145. | |
| |
11. Meissburger B., Stachorski L., Roder E. et al. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) controls adipogenesis in obesity in mice and in humans. Diabetologia, 2011; 54(6): 1468-1479. | |
| |
12. Dews M., Homayouni A., Yu D. et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nature Genetics, 2006; 38(9):1060-1065. | |
| |
13. Hashimoto G., Inoki I., Fujii Y. et al. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. The Journal of Biological Chemistry, 2002; 277(39): 36288-36295. | |
| |
14. Meissburger B., Ukropec J., Roeder E. et al. Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma. EMBO Molecular Medicine, 2011; 3(11): 637-651. | |
| |
15. Hattori N., Carrino D.A., Lauer M.E. et al. Pericellular versican regulates the fibroblast-myofibroblast transition: a role for ADAMTS5 protease-mediated proteolysis. The Journal of Biological Chemistry, 2011; 286(39): 34298-34310. | |
| |
16. Bi X., Pohl N.M., Qian Z. et al. Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice. Carcinogenesis, 2012; 33(2): 326-330. | |
| |
17. Iozzo R.V., Buraschi S., Genua M. et al. Decorin antagonizes IGF receptor I (IGF-IR) function by interfering with IGF-IR activity and attenuating downstream signaling. The Journal of Biological Chemistry, 2011; 286(40): 34712-34721. | |
| |
18. Nikitovic D., Chalkiadaki G., Berdiaki A. et al. Lumican regulates osteosarcoma cell adhesion by modulating TGFbeta2 activity. International Journal of Biochemistry and Cell Biology, 2011; 43(6): 928-935. | |
| |
19. Franklin A.J., Jetton T.L., Shelton K.D., Magnuson M.A. BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription. Molecular and Cellular Biology, 1994; 14(10): 6773-6788. | |
| |
20. Waltenberger J. VEGF resistance as a molecular basis to explain the angiogenesis paradox in diabetes mellitus. Biochemical Society Transactions, 2009; 37(Pt. 6): 1167-1170. | |
| |
21. Aragón T., van Anken E., Pincus D. et al. Messenger RNA targeting to endoplasmic reticulum stress signalling sites. Nature, 2009; 457(7230): 736-740. | |
| |
22. Acosta-Alvear D., Zhou Y., Blais A. et al. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Molecular Cell, 2007; 27: 53-66. | |
| |
23. Drogat B., Auguste P., Nguyen D.T. et al. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Research, 2007; 67(14): 6700-6707. | |
| |
24. Lombardi A., Ulianich L., Treglia A.S. et al. Increased hexosamine biosynthetic pathway flux dedifferentiates INS-1E cells and murine islets by an extracellular signal-regulated kinase (ERK)1/2-mediated signal transmission pathway. Diabetologia, 2012; 55(1): 141-153. | |
| |
25. John A.S., Hu X., Rothman V.L., Tuszynski G.P. Thrombospondin-1 (TSP-1) up-regulates tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human tumor cells: exploring the functional significance in tumor cell invasion. Experimental and Molecular Pathology, 2009; 87(3):184-188. |
Refbacks
- There are currently no refbacks.
Copyright (c) 2012 Studia biologica
This work is licensed under a Creative Commons Attribution 4.0 International License.