Different effects of simvastatin on keloid fibroblasts under hypoxia and TGF-β1 treatment
10.3760/cma.j.issn.1009-4598.2016.02.012
- VernacularTitle:辛伐他汀对不同病理条件刺激的瘢痕疙瘩成纤维细胞功能的影响
- Author:
Bin CHEN
1
;
Chunfu KANG
;
Dongning YU
;
Xia ZHAO
;
Yang AN
;
Zelian QIN
Author Information
1. 100191,北京大学第三医院成形外科
- Keywords:
Simvastatin;
Keloid;
Fibroblast
- From:
Chinese Journal of Plastic Surgery
2016;32(2):130-135
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of simvastatin on the proliferation,apoptosis and protein expressions of keloid fibroblasts under normoxia,hypoxia or TGF-β1 treatment.Methods Keloid fibroblasts (KFs) were isolated by explants culture method.KFs were treated with different concentrations of simvastatin under normoxia or hypoxia (2％ O2) for 24 h and 48 h.The effects of simvastatin on cell proliferation were detected by CCK-8.Flow cytometer was used to detect the apoptosis of KFs treated with 10 μ mol/L simvastatin for 24 h or 48 h under normoxia,hypoxia or 10 ng/ml TGF-β1 treatment.Then the expressions of keloid-related proteins were analyzed by Western Blot.Results It showed that simvastatin could inhibit the proliferation of KFs in a concentration-and time-dependent manner with the concentration range of 10-500 μ mol/L for 24 h and 0.1-500 μ mol/L for 48 h.This inhibitory effect could be significantly enhanced when cells were incubated under hypoxia for 48h with 10-500 μ mol/L simvastatin.10 μ mol/L simvastatin could not influence the apoptosis of KFs under normoxia or TGF-β1 treatment,neither incubated for 24 h nor 48 h.When incubated under hypoxia,10 μ mol/L simvastatin could significantly induce the apoptosis of KFs,with the rate of 155.6％ for 24 h and 478.8％ for 48 h,compared with no-drug control.There are no significant influences on the expression of type Ⅰ collagen,CTGF or TIMP-1 when KFs were treated with 10 μ mol/L simvastatin under normoxia for 48 h.When incubated with 10 ng/ml TGF-β1 together with 10 μmol/L simvastatin for 48 h,the expression of CTGF was significantly inhibited.KFs treated with 10 μ mol/L simvastatin under hypoxia for 48 h showed a significant decrease of type Ⅰ collagen and CTGF,and a significant increase of TIMP-1.Conclusions Simvastatin has different effects on the proliferation,apoptosis and protein expressions of KFs in a dosedependent manner under different conditions.The effects are enhanced under hypoxia.
