Zavala J, Treviño V, Reyna-Fuentes AA, Arellano-Gurrola CM, Enriquez-Ochoa D, Domene-Hickman JL, Valdez-García JE

Language: Spanish
References: 23
Page: 7-13
PDF size: 281.66 Kb.

ABSTRACT

Purpose: To compare the gene expression associated with lipid and cholesterol metabolism in pterygium fibroblasts, adipocytes and other types of fibroblasts. Methodology: Gene expression data from 12 samples of primary pterygium, 12 from adipose cells and 63 from other types of fibroblasts with the same platform were obtained from the gene expression omnibus database. The mean expression for each gene was calculated for each cell type. Differentially and similarly expressed genes were subjected to overrepresentation analysis to obtain signaling pathways, protein interactions, and associated functional terms. Results: Of the 16,511 genes analyzed, 921 differentially and 1,207 similarly expressed were found. From the overrepresentation analysis of differentially expressed genes, 460 genes were found associated (p ‹ 0.05) to the SREBP1 protein, while in the similarly expressed genes 615 were found associated to the same protein. The HMGCR, ACOX1 and LRP1 genes showed significantly decreased expression (p ‹ 0.05) in pterygium fibroblasts compared to adipocytes and other types of fibroblasts. Expression of the HMGCS gene was significantly higher (p ‹ 0.05) in pterygium fibroblasts than in adipocytes and lower than in other fibroblast types. Other genes, including LPL, ACAT1, LSS, LDLR and LCAT showed a differential expression between the three cell types. Conclusion: Deregulated expression of genes associated with lipid and cholesterol metabolism in pterygium fibroblasts is related to proliferation, suggesting further study as potential therapeutic targets.

REFERENCES

1. Mohammed I. Treatment of pterygium. Ann Afr Med. 2011;10:197-203.

2. Cardenas-Cantu E, Zavala J, Valenzuela J, Valdez-Garcia JE. Molecular Basis of Pterygium Development. Semin Ophthalmol. 2016;31:567-83.

3. Hacioglu D, Erdol H. Developments and current approaches in the treatment of pterygium. Int Ophthalmol. 2017;37:1073-81.

4. Peiretti E, Dessi S, Mulas MF, Abete C, Galantuomo MS, Fossarello M. Fibroblasts isolated from human pterygia exhibit altered lipid metabolism characteristics. Exp Eye Res. 2006;83:536-42.

5. Galantuomo M, Mulas MF, Baire P, Abete C, Peiretti E, Dessì S, et al. Proliferative Activity and Cholesterol Ester Metabolism in Primary Culture of Human Pterygium Fibroblasts. Invest Ophthalmol Vis Sci. 2005;46:960.

6. Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37:1-13.

7. Haung DW, Sherman BT, Lempicli RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatic resources. Nat Protoc. 2009;4:44-57.

8. Tong L, Chew J, Yang H, Ang LPK, Tan DTH, Beuerman RW. Distinct gene subsets in pterygia formation and recurrence: dissecting complex biological phenomenon using genome wide expression data. BMC Med Genomics. 2009;2:14.

9. Peiretti E, Dessi S, Putzolu M, Fossarello M. Hyperexpression of low-density lipoprotein receptors and hydroxy-methylglutaryl-coenzyme A-reductase in human pinguecula and primary pterygium. Invest Ophthalmol Vis Sci. 2004;45:3982-5.

10. Shimozawa N. Molecular and clinical aspects of peroxisomal diseases. J Inherit Metab Dis. 2007;30:193-7.

11. Arnaud C, Veillard NR, Mach F. Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5: 127-34.

12. Gordts PL, Reekmans S, Lauwers A, Van Dongen A, Verbeek L, Roebroek AJ. Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:1258-64.

13. Raeder MB, Ferno J, Glambek M, Stansberg C, Steen VM. Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006;395:185-90.

14. Farese RV Jr, Linton MF, Young SG. Apolipoprotein B gene mutations affecting cholesterol levels. J Intern Med. 1992;231:643-52.

15. Berbée JFP, van der Hoogt CC, Sundararaman D, Havekes LM, Rensen, PCN. Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL. J Lipid Res. 2005;46:297-306.

16. Duchateau PN, Movsesyan I, Yamashita S, Sakai N, Hirano KI, Schoenhaus SA, et al. Plasma apolipoprotein L concentrations correlate with plasma triglycerides and cholesterol levels in normolipidemic, hyperlipidemic, and diabetic subjects. J Lipid Res. 2000;41:1231-6.

17. Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2000;1:507-37.

18. Okubo M, Horinishi A, Saito M, Ebara T, Endo Y, Kaku K, et al. A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency. Mol Genet Metab. 2007;92:229-33.

19. Ossoli A, Simonelli S, Vitali C, Franceschini G, Calabresi L. Role of LCAT in Atherosclerosis. J Atheroscler Thromb. 2016;23:119-27.

20. Hastings N, Agaba M, Tocher DR, Leaver MJ, Dick JR, Sargent JR. A vertebrate fatty acid desaturase with Δ5 and Δ6 activities 2001;25:14304-9.

21. Plaisier CL, Horvath S, Huertas-Vazquez A, Cruz-Bautista I, Herrera MF, Tusie-Luna T. A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia. PLoS Genet. 2009;5:e1000642.

22. Huang MC, Chang WT, Chang HY, Chung HF, Chen FP, Huang YF, et al. FADS Gene Polymorphisms, Fatty Acid Desaturase Activities, and HDL-C in Type 2 Diabetes. Int J Environ Res Public Health. 2017;14:E572.

23. Fujita M, Momose A, Ohtomo T, Nishinosono A, Tanonaka K, Toyoda H, et al. Upregulation of fatty acyl-CoA thioesterases in the heart and skeletal muscle of rats fed a high-fat diet. Biol Pharm Bull. 2011;34:87-91.