siRNA against plasminogen activator inhibitor-1 ameliorates bleomycin-induced lung fibrosis in rats
siRNA against plasminogen activator inhibitor-1 ameliorates bleomycin-induced lung fibrosis in rats
复制标题
针对纤溶酶原激活剂抑制剂-1 的 siRNA 可改善博莱霉素诱导的大鼠肺纤维化
DOI：
10.1038/aps.2012.39
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发表时间：
2012-06
影响因子：
8.2
通讯作者：
Zhang, Min
中科院分区：
文献类型：
--
作者：
Zhang, Yan-ping;Li, Wen-bin;Wang, Wei-li;Liu, Jian;Song, Shu-xia;Bai, Lin-lin;Hu, Yu-yan;Yuan, Ya-dong;Zhang, Min
目的：纤溶酶原激活物抑制剂 -1（PAI -1）参与肺纤维化的进展。本研究旨在探讨用小干扰RNA（siRNA）沉默PAI -1表达对肺纤维化的影响，并进行评估
Aim:Plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. The present study was undertaken to examine the effects on pulmonary fibrosis of silencing PAI-1 expression with small interfering RNA (siRNA) and to assess the possible underlying mechanisms.Methods:Male Wistar rats were subjected to intratracheal injection of bleomycin (BLM, 5 mg/kg, 0.2 mL) to induce pulmonary fibrosis. Histopathological changes of lung tissue were examined with HE or Masson's trichrome staining. The expression levels of α-smooth muscle actin (α-SMA), collagen type-I and type-III, caspase-3, as well as p-ERK1/2 and PI3K/Akt in the lung tissue were evaluated using imunohistochemistry and Western blot analyses. The fibroblasts isolated from BLM-induced fibrotic lung tissue were cultured and transfected with pcDNA-PAI-1 or PAI-1siRNA. The expression level of PAI-1 in the fibroblasts was measured using real time RT-PCR and Western blot analysis. The fibroblast proliferation was evaluated using MTT assay.Results:Intratracheal injection of PAI-1-siRNA (7.5 nmoL/0.2 mL) significantly alleviated alveolitis and collagen deposition, reduced the expression of PAI-1, α-SMA, collagen type-I and collagen type-III, and increased the expression of caspase-3 in BLM-induced fibrotic lung tissue. In consistence with the in vivo results, the proliferation of the cultured fibroblasts from BLM-induced fibrotic lung tissue was inhibited by transfection with PAI-1-siRNA, and accelerated by overexpression of PAI-1 by transfection with pcDNA-PAI-1. The expression of caspase-3 was increased as a result of PAI-1 siRNA transfection, and decreased after transfection with pcDNA-PAI-1. In addition, the levels of p-ERK1/2 and PI3K/Akt in the fibrogenic lung tissue were reduced after treatment with PAI-1siRNA.Conclusion:The data demonstrate that PAI-1 siRNA inhibits alveolitis and pulmonary fibrosis in BLM-treated rats via inhibiting the proliferation and promoting the apoptosis of fibroblasts. Suppression ERK and AKT signalling pathways might have at least partly contributed to this process. Targeting PAI-1 is a promising therapeutic strategy for pulmonary fibrosis.
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DOI：
10.1083/jcb.200207070
发表时间：
2002-12-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ma Z;Thomas KS;Webb DJ;Moravec R;Salicioni AM;Mars WM;Gonias SL
通讯作者：
Gonias SL
DOI：
10.1201/b13341-74
发表时间：
--
期刊：
--
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
J. Aguirre-Ghiso;Y. Estrada;David Liu;L. Ossowski
通讯作者：
J. Aguirre-Ghiso;Y. Estrada;David Liu;L. Ossowski
影响因子：
4.9
作者：
Durcan, Niamh;Murphy, Charlotte;Cryan, Sally-Ann
通讯作者：
Cryan, Sally-Ann
影响因子：
2.6
作者：
Jason S. Zolak;J. D. de Andrade
通讯作者：
Jason S. Zolak;J. D. de Andrade