Mevastatin inhibits the differentiation of thyroid-associated ophthalmopathy derived orbital preadipocytes.
10.3969/j.issn.1672-7347.2010.05.017
- Author:
Wenshu YI
1
;
Xueliang XU
Author Information
1. Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Adipocytes;
pathology;
Adipose Tissue;
pathology;
Cell Differentiation;
drug effects;
Cells, Cultured;
Depression, Chemical;
Graves Ophthalmopathy;
pathology;
Humans;
Lovastatin;
analogs & derivatives;
pharmacology;
Orbit;
PPAR gamma;
antagonists & inhibitors;
genetics;
metabolism;
RNA, Messenger;
genetics;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2010;35(5):511-517
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of mevastatin (Mev) on the expression of peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) mRNA and differentiation of Thyroid-associated ophthalmopathy (TAO) derived orbital preadipocytes in vitro.
METHODS:Orbital adipose tissues were obtained from TAO patients undergoing orbital decompression surgery. The orbital preadipocytes cultured from the orbital adipose tissues were divided into Group A (a control group) and Group B (an intervention group). Group B was subdivided into Group B1-B5, all groups were stimulated to differentiate into mature adipocytes with cocktail differentiation medium.The entire course of differentiation was 10 d. The differentiation of orbital preadipocytes in Group A was induced with routine inducer,while at in Group B1,B2, and B3 was interfered with 5 micromol/L (B1), 10 micromol/L(B2),20 micromol/L (B3) mevastatin respectively during the whole process of differentiation. The differentiation of orbital preadipocytes in Group B4 and B5 was interfered with 10 micromol/L mevastatin day 4 (B4) or day 8 (B5) of the differentiation process until the entire course was over. Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining. The value of optical absorption was measured at 492 nm with enzyme-linked immunosorbent assay. The expression of PPAR-gamma mRNA was detected by reverse transcription polymerase chain reaction.
RESULTS:The light absorption value (A) and PPAR-gamma mRNA expression of differentiated cells in Group A,B1,B2,and B3 decreased successively,and there was significant difference in any of the 2 groups among Group A, B1 and B2, and B3 (P<0.05). The value A and PPAR-gamma mRNA expression of differentiated cells in Group A, B4, and B2 decreased successively, and the difference in any of the 2 groups among these 3 groups was significant. However, there were no significant difference between Group A and B5.
CONCLUSION:Mevastatin inhibits the differentiation of TAO derived orbital preadipocytes by blocking PPAR-gamma mRNA expression. The degree of inhibition is not only concentration-dependent but also associated with the stage of differentiation. The earlier the differentiation, the stronger the inhibition.
