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E. Peiretti, S. Dessì, C. Norfo, C. Mulas, C. Abete, S. Galantuomo, I. Zucca, M. Fossarello; mRNA Level Alterations of Proteins Involved in Cholesterol Esters Metabolism in Pterygium Fibroblasts . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4982.
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Our previous studies raised the possibility that alterations in cholesterol metabolism, mainly in cholesterol esterification, may have a role in regulating the growth rate of fibroblasts isolated from patients with pterygium. To further assess such a possibility, in the present study we measured the mRNA levels of proteins involved in cholesterol esters metabolism: 1) acyl–coenzyme A cholesterol acyltransferase (ACAT), which is the enzyme responsible for intracellular cholesterol ester formation; 2) multidrug resistance protein (MDR), which has been implicated in cholesterol transport from the plasma membrane to the ER(Endoplasmic reticulum) ; 3) caveolin–1, the key structural protein of caveolae, a suggested possible carrier of excess cholesterol from the ER to the caveolae–plasma membrane, 4) neutral cholesterol ester hydrolase (nCEH), the enzyme responsible for the hydrolysis of cholesterol esters and 5) ABCA1, the receptor that mediates cholesterol efflux. In addition, in the same cells we also evaluated the effect on the above parameters of two potent antiproliferative : everolimus (EVE)and pioglitazone (PIO).
mRNA levels were determined in normal conjunctival fibroblasts (NCF) and primary pterygium fibroblasts (PF) by RT–PCR.
An increased expression of ACAT1 and MDR1 associated with reduced mRNA levels of caveolin–1, nCEH and ABCA1 was demonstrated in PF. These alterations were partially reverted by the treatment of cells with EVE and PIO .
Collectively these data add new support for the concept that intracellular alterations of cholesterol ester metabolism may be involved in the progression of pteygium and raise the possibility that MDR1, ACAT1, caveolin–1 nCEH and ABCA1 gene expression may emerge as new targets for diagnosis, prevention and cure of such disease.
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