Angiopoietin-1 protects against endotoxin-induced neonatal lung injury and alveolar simplification in mice.
Angiopoietin-1 protects against endotoxin-induced neonatal lung injury and alveolar simplification in mice.
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DOI：
10.1038/s41390-021-01544-0
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发表时间：
2022-05
影响因子：
3.6
通讯作者：
Sampath V
中科院分区：
文献类型：
--
作者：
Salimi U;Menden HL;Mabry SM;Xia S;Sampath V
早产儿败血症是支气管肺发育不良（BPD）的危险因素，但肺损伤的潜在机制尚不清楚。内皮细胞（EC）血管生成素2（ANGPT 2）的异常表达破坏血管生成素1（ANGPT 1）/TIE 2介导的内皮静止，并与成人脓毒症诱导的急性呼吸窘迫综合征有关。我们假设重组ANGPT 1将减轻脓毒症诱导的ANGPT 2表达、炎症、急性肺损伤（ALI）和囊状肺中的肺泡重塑。在人肺微血管内皮细胞（HPMEC）中评价重组ANGPT 1对脂多糖（LPS）诱导的内皮炎症的影响。在暴露于腹腔内LPS和重组ANGPT 1预处理的新生小鼠中评估ALI和长期肺泡重塑。LPS使EC TIE 2去磷酸化与体内和体外ANGPT 2增加相关。ANGPT 1抑制LPS和ANGPT 2诱导的HPMEC EC炎症。用LPS处理的新生小鼠肺细胞因子表达增加，嗜中性粒细胞流入和细胞凋亡。ANGPT 1预处理抑制LPS诱导的肺Toll样受体信号传导、炎症和ALI。ANGPT 1可缓解LPS诱导的金属蛋白酶9表达和弹性纤维断裂的急性增加，以及径向肺泡计数的长期减少。在脓毒症诱导的BPD实验模型中，ANGPT 1保持内皮静止，抑制ALI，并抑制肺泡简化。
Sepsis in premature newborns is a risk factor for bronchopulmonary dysplasia (BPD), but underlying mechanisms of lung injury remain unclear. Aberrant expression of endothelial cell (EC) angiopoietin 2 (ANGPT2) disrupts angiopoietin 1 (ANGPT1)/TIE2-mediated endothelial quiescence, and is implicated in sepsis-induced acute respiratory distress syndrome in adults. We hypothesized that recombinant ANGPT1 will mitigate sepsis-induced ANGPT2 expression, inflammation, acute lung injury (ALI), and alveolar remodeling in the saccular lung. Effects of recombinant ANGPT1 on lipopolysaccharide (LPS)-induced endothelial inflammation were evaluated in human pulmonary microvascular endothelial cells (HPMEC). ALI and long-term alveolar remodeling were assessed in newborn mice exposed to intraperitoneal LPS and recombinant ANGPT1 pretreatment. LPS dephosphorylated EC TIE2 in association with increased ANGPT2 in vivo and in vitro. ANGPT1 suppressed LPS and ANGPT2-induced EC inflammation in HPMEC. Neonatal mice treated with LPS had increased lung cytokine expression, neutrophilic influx, and cellular apoptosis. ANGPT1 pre-treatment suppressed LPS-induced lung Toll-like receptor signaling, inflammation, and ALI. LPS-induced acute increases in metalloproteinase 9 expression and elastic fiber breaks, as well as a long-term decrease in radial alveolar counts, were mitigated by ANGPT1. In an experimental model of sepsis-induced BPD, ANGPT1 preserved endothelial quiescence, inhibited ALI, and suppressed alveolar simplification.
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影响因子：
8.8
作者：
David S;Mukherjee A;Ghosh CC;Yano M;Khankin EV;Wenger JB;Karumanchi SA;Shapiro NI;Parikh SM
通讯作者：
Parikh SM
影响因子：
6.9
作者：
Houghton, A. McGarry
通讯作者：
Houghton, A. McGarry
DOI：
10.1152/ajplung.00230.2011
发表时间：
2012-05-01
影响因子：
4.9
作者：
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通讯作者：
Alvira, Cristina M.
影响因子：
9.6
作者：
OGDEN, BE;MURPHY, S;JOHNSON, JD
通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
McDonald, Donald M.