Peroxisome proliferator-activated receptor γ agonists reduce cell proliferation and viability and increase apoptosis in systemic sclerosis fibroblasts

Peroxisome proliferator-activated receptor γ agonists reduce cell proliferation and viability and increase apoptosis in systemic sclerosis fibroblasts
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DOI:
10.1111/j.1365-2133.2012.11199.x
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发表时间:
2013-01-01
影响因子:
10.3
通讯作者:
Fallahi, P.
Fallahi, P.
中科院分区:
医学1区
文献类型:
--
作者:
Antonelli, A.;Ferri, C.;Fallahi, P.

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背景没有研究评估过氧化物酶体增殖物激活受体γ(PPAR γ)激动剂对细胞活力的影响,目的观察两种纯的PPAR γ激动剂对体外培养的系统性硬化症(SSc)成纤维细胞增殖和凋亡的影响。观察罗格列酮和吡格列酮对体外培养的SSc成纤维细胞的作用,并与对正常成纤维细胞的作用进行比较(基于四唑鎓盐的裂解和细胞增殖试剂WST-1的吸光度的测量),以及细胞凋亡的测定结果罗格列酮或吡格列酮组的细胞凋亡率明显高于对照组(20 μ mol L-1)显著降低细胞增殖(2小时后,与基线相比,细胞计数分别为75%和83%)和细胞活力(2小时后,与基线相比,吸光度分别降低25%和22%),并增加细胞凋亡(孵育48小时后凋亡细胞百分比分别为9.9%和8.6%),结论罗格列酮或吡格列酮对SSc成纤维细胞的影响提高了对受SSc影响的患者中PPAR γ激动剂的治疗作用的假设。
Background No study has evaluated the effect of the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists on cell viability, proliferation and apoptosis in cultured systemic sclerosis (SSc) fibroblasts.Objectives The effects of two pure PPAR gamma agonists (rosiglitazone and pioglitazone) in cultured SSc fibroblasts were evaluated and compared with effects in normal fibroblasts.Methods The study included evaluation of cell viability and proliferation (based on the cleavage of tetrazolium salts and measurement of absorbance of the cell proliferation reagent WST-1), and determination of cell apoptosis (by means of the Hoechst dye uptake).Results Rosiglitazone or pioglitazone (20 mu mol L-1) significantly reduced cell proliferation (cell count of 75% and 83% compared with baseline, respectively, after 2 h) and cell viability (absorbance reductions of 25% and 22% compared with baseline, respectively, after 2 h), and increased apoptosis (apoptotic cell percentages 9.9% and 8.6%, respectively, after 48 h of incubation) in SSc fibroblasts, whereas they did not present a significant influence on control fibroblasts.Conclusions The effects of rosiglitazone or pioglitazone shown on SSc fibroblasts raise the hypothesis of a therapeutic role for PPAR gamma agonists in patients affected by SSc.