期刊
RESPIRATORY RESEARCH
卷 20, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12931-019-1099-6
关键词
Acute lung injury; Endothelial progenitor cells; Reverse D-4F; Apolipoprotein A-I; Endothelial nitric oxide synthase
资金
- National Natural Science Foundation of China [81600360, 91539114, 81370381, 31401258]
- Province Natural Science Foundation of Shandong [ZR2012HL18]
- Province Science and Technology Development Foundation of Shandong [2014GSF118105]
- Taishan Scholars Foundation of Shandong Province [ts201511057]
- Province Higher University Science and Technology Development Project of Shandong [J14LK03]
- Province Medical Science and Technology Development Project of Shandong [2017WSB32011]
BackgroundPatients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model.MethodsLPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved.ResultsRev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF- and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS.ConclusionsThese findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway.
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