PGC1-Alpha/Sirt3 Signaling Pathway Mediates the Anti-Pulmonary Fibrosis Effect of Hirudin by Inhibiting Fibroblast Senescence

被引:2
作者
He, Bin [1 ,2 ]
Zeng, Qian [2 ]
Tian, Yumei [1 ]
Luo, Yuyang [2 ]
Liao, Minlin [2 ]
Huang, Wenjie [1 ]
Wu, Bin [1 ]
Luo, Ziqiang [3 ]
Huang, Xiaoting [2 ]
Liu, Wei [2 ]
Tang, Siyuan [2 ]
机构
[1] Hunan Univ Med, Sch Nursing, Huaihua 418000, Peoples R China
[2] Cent South Univ, Xiangya Nursing Sch, Changsha 410013, Peoples R China
[3] Cent South Univ, Xiangya Sch Med, Changsha 410013, Peoples R China
关键词
idiopathic pulmonary fibrosis; hirudin; fibroblast senescence; PGC1-alpha/Sirt3; pathway; CELLULAR SENESCENCE; OXIDATIVE STRESS; THROMBIN; INFLAMMATION; MECHANISMS; GENERATION; APOPTOSIS; RECEPTOR; PROTEIN; INJURY;
D O I
10.3390/biomedicines12071436
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease for which there is a lack of effective pharmacological treatments. Hirudin, a natural peptide extracted from leeches, has been used for broad pharmacological purposes. In this study, we investigated the therapeutic effects of hirudin on IPF and its related mechanism of action. By constructing a mouse model of pulmonary fibrosis and treating it with hirudin in vivo, we found that hirudin exerted anti-fibrotic, anti-oxidative, and anti-fibroblast senescence effects. Moreover, using an in vitro model of stress-induced premature senescence in primary mouse lung fibroblasts and treating with hirudin, we observed inhibition of fibroblast senescence and upregulation of PGC1-alpha and Sirt3 expression. However, specific silencing of PGC1-alpha or Sirt3 suppressed the anti-fibroblast senescence effect of hirudin. Thus, the PGC1-alpha/Sirt3 pathway mediates the anti-fibroblast senescence effect of hirudin, potentially serving as a molecular mechanism underlying its anti-fibrosis and anti-oxidative stress effects exerted on the lungs.
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页数:15
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