Regulation of PINX1 expression ameliorates lipopolysaccharide-induced lung injury and alleviates cell senescence during the convalescent phase through affecting the telomerase activity

调节PINX1表达通过影响端粒酶活性改善脂多糖引起的肺损伤并减轻恢复期细胞衰老

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作者:Shujing Li, Bin Jiang, Haiyang Yu, Dongqing Song

Abstract

PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) is necessary for telomerase reverse transcriptase (TERT) elements to bind at telomeres and non-telomere sites. We aimed to investigate the role of PINX1 and TERT in lipopolysaccharide (LPS)-induced lung injury during acute stage and convalescent phase. Lung injury rat model was induced, and the expression of PINX1 and TERT in serum and lung tissues was examined using RT-qPCR on day 0 (D0), D3, and D14, respectively. The pathologic changes of lung tissues on D3 and D14 were detected using hematoxylin and eosin staining after TERT overexpression, PINX1 overexpression, or PINX1 silencing in lung injury rats. Results revealed that TERT was persistently reduced on D3 and D14, while PINX1 was decreased on D3 but increased on D14. TERT overexpression and PINX1 silencing led to the most serious lung damage, the highest levels of inflammatory factors and apoptosis on D3, while the best recovery was observed on D14. Simultaneously, PINX1 overexpression presented the opposite effects at acute stage and convalescent phase. Co-immunoprecipitation (co-IP) assay verified the connection between PINX1 and TERT. Taken together, these findings demonstrated that regulation of PINX1 expression ameliorates lung injury and alleviates cell senescence during the convalescent phase through affecting the telomerase activity.

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