Phosphatidylethanolamine Induces an Antifibrotic Phenotype in Normal Human Lung Fibroblasts and Ameliorates Bleomycin-Induced Lung Fibrosis in Mice

被引:25
作者
Vazquez-de-Lara, Luis G. [1 ]
Tlatelpa-Romero, Beatriz [1 ]
Romero, Yair [1 ]
Fernandez-Tamayo, Nora [1 ]
Vazquez-de-Lara, Fernando [1 ]
Justo-Janeiro, Jaime M. [2 ]
Garcia-Carrasco, Mario [1 ]
de-la-Rosa Paredes, Rene [2 ]
Cisneros-Lira, Jose G. [3 ]
Mendoza-Milla, Criselda [3 ]
Moccia, Francesco [4 ]
Berra-Romani, Roberto [1 ]
机构
[1] Benemerita Univ Autonoma Puebla, Fac Med, Puebla 72410, Mexico
[2] Hosp Gen Sur, Puebla 72490, Mexico
[3] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Mexico City 14080, DF, Mexico
[4] Univ Pavia, Dept Biol & Biotechnol Lazzaro Spallanzani, Lab Gen Physiol, I-27100 Pavia, Italy
关键词
pulmonary surfactant; phosphatidylethanolamine; lung fibrosis; bleomycin model; lung fibroblasts; Ca2+ signaling; PULMONARY SURFACTANT; GENE-EXPRESSION; COLLAGEN; CELLS; OSCILLATIONS; INVOLVEMENT; ADSORPTION; APOPTOSIS; TARGETS; INJURY;
D O I
10.3390/ijms19092758
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
Lung surfactant is a complex mixture of phospholipids and specific proteins but its role in the pathogenesis of interstitial lung diseases is not established. Herein, we analyzed the effects of three representative phospholipid components, that is, dipalmitoilphosphatidylcoline (DPPC), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE), on collagen expression, apoptosis and Ca2+ signaling in normal human lung fibroblasts (NHLF) and probed their effect in an experimental model of lung fibrosis. Collagen expression was measured with RT-PCR, apoptosis was measured by using either the APOPercentage assay kit (Biocolor Ltd., Northern Ireland, UK) or the Caspase-Glo 3/7 assay (Promega, Madison, WI, USA) and Ca2+ signaling by conventional epifluorescence imaging. The effect in vivo was tested in bleomycin-induced lung fibrosis in mice. DPPC and PG did not affect collagen expression, which was downregulated by PE. Furthermore, PE promoted apoptosis and induced a dose-dependent Ca2+ signal. PE-induced Ca2+ signal and apoptosis were both blocked by phospholipase C, endoplasmic reticulum pump and store-operated Ca2+ entry inhibition. PE-induced decrease in collagen expression was attenuated by blocking phospholipase C. Finally, surfactant enriched with PE and PE itself attenuated bleomycin-induced lung fibrosis and decreased the soluble collagen concentration in mice lungs. This study demonstrates that PE strongly contributes to the surfactant-induced inhibition of collagen expression in NHLF through a Ca2+ signal and that early administration of Beractant enriched with PE diminishes lung fibrosis in vivo.
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页数:16
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