Rosiglitazone attenuates activation of human Tenon's fibroblasts induced by transforming growth factor-β1.
OBJECTIVE
To investigate the influence of rosiglitazone on activation of human Tenon's fibroblasts (HTFs) and to access the possible mechanism.


METHODS
Cultured human Tenon's fibroblasts were pretreated in two different concentrations of rosiglitazone (5 μmol/l and 10 μmol/l) before being stimulated with 5 ng/ml transforming growth factor β1 (TGF-β1). The viability and proliferation of cells were accessed by cell count kit-8 assay; Cell migration was examined by the wound closure assay; Alpha smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) and type I collagen (COL I) transcription were detected by RT-qPCR; The expression and localization of α-SMA protein were examined by Western-blot analysis and Immunofluorescence staining; Western-blot analysis was also used to check the expression of CTGF, COL I peroxisome proliferator-activated receptor gamma (PPAR-γ), and phosphorylation of the signaling protein Smad2/3


RESULTS
Rosiglitazone is able to attenuate the up-regulation of α-SMA, CTGF, and COL I transcription, as well as affect protein expression, proliferation, and migration of cells; rosiglitazone also can increase PPAR-γ expression and attenuate Smad2/3 phosphorylation.


CONCLUSIONS
Rosiglitazone can effectively attenuate activation of HTFs induced by TGF-β1 without obvious toxicity. The possible mechanism might be that rosiglitazone interferes with TGF-β/Smad signaling pathway.
Department of Ophthalmology, People's Hospital of Hebei Province, Hebei, Shijiazhuang, 050051, People's Republic of China.
Fang
F
Fan
Yuehua
Y
Li
Xuanchu
X
Duan
Tantai
T
Zhao
Dongning
D
Pan
Huihui
H
Chen
D000199:Actins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007004:Hypoglycemic Agents / Q000633:toxicity*; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077154:Rosiglitazone; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D058475:Tenon Capsule / Q000166:cytology*; D045162:Thiazolidinediones / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation
C541116:ACTA2 protein, human; D000199:Actins; C526317:CCN2 protein, human; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor