Endotoxin-induced acute lung injury in mice with postnatal deletion of nephronectin.
Endotoxin-induced acute lung injury in mice with postnatal deletion of nephronectin.
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DOI：
10.1371/journal.pone.0268398
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肺的急性损伤涉及上皮及其下层细胞外基质（ECM）、基底膜（BM）的损伤。BM如何有助于损伤解决的了解甚少。肾连蛋白（NPNT）是整联蛋白α8β1的高亲和力配体，尽管首次在小鼠肾脏中发现，但主要在肺中表达，并定位于肺泡中的BM。为了确定NPNT是否在肺的急性损伤和炎症中起作用，我们使用具有Npnt的floxed等位基因的小鼠与在ROSA位点表达的他莫昔芬诱导型Cre重组酶组合，开发了NPNT的出生后缺失模型。在他莫昔芬处理的Cre+动物的肺中，NPNT的表达显著降低。Cre+小鼠和Cre-对照组给予E. coli LPS诱导的损伤和炎症反应。在Cre-肺中，尽管Npnt和Itga 8（整合素α8）转录物在炎症高峰时下调，但仍可检测到NPNT蛋白。虽然Cre+和Cre-的炎症发作相似，但NPNT缺乏的肺仍具有增厚的肺泡隔，并且在消退期支气管肺泡灌洗液（BALF）中存在增加的巨噬细胞。在体外实验中，来自Cre+肺的BALF对骨髓源性巨噬细胞的趋化性比Cre-强，但在体内对趋化因子的阐述方面没有差异。我们推测，在该模型中，肺泡BM中NPNT的缺乏损害或延迟炎症和损伤的消退，但需要进一步研究来确定NPNT在组织修复中的确切作用。
Acute injury of the lung involves damage to the epithelium and its underlying extracellular matrix (ECM), the basement membrane (BM). How BMs contribute to injury resolution is poorly understood. Nephronectin (NPNT) is a high-affinity ligand for integrin α8β1 and, although first identified in the mouse kidney, is prominently expressed in the lung, where it localizes to BMs in the alveoli. To determine if NPNT plays a role in acute injury and inflammation of the lung, we developed a model for postnatal deletion of NPNT using mice with a floxed allele of Npnt in combination with a tamoxifen-inducible Cre recombinase expressed at the ROSA locus. Expression of NPNT was substantially reduced in lungs from tamoxifen-treated Cre+ animals. Cre+ mice and Cre- controls were given E. coli LPS by oropharyngeal aspiration to induce injury and inflammation. In Cre- lungs, although both Npnt and Itga8 (integrin α8) transcripts were downregulated at the peak of inflammation, NPNT protein was still detectable. While the onset of inflammation was similar for Cre+ and Cre-, NPNT-deficient lungs still had thickened alveolar septa and there were increased macrophages in the bronchoalveolar lavage fluid (BALF) in the resolution phase. BALF from Cre+ lungs was more chemotactic for bone marrow-derived macrophages than Cre- in in vitro experiments, but there were no differences in the elaboration of chemokines in vivo. We speculate that absence of NPNT in BMs of the alveoli impairs or delays inflammatory and injury resolution in this model, but further studies are needed to establish the precise role of NPNT in tissue repair.
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影响因子：
16.6
作者：
Soler Artigas M;Wain LV;Miller S;Kheirallah AK;Huffman JE;Ntalla I;Shrine N;Obeidat M;Trochet H;McArdle WL;Alves AC;Hui J;Zhao JH;Joshi PK;Teumer A;Albrecht E;Imboden M;Rawal R;Lopez LM;Marten J;Enroth S;Surakka I;Polasek O;Lyytikäinen LP;Granell R;Hysi PG;Flexeder C;Mahajan A;Beilby J;Bossé Y;Brandsma CA;Campbell H;Gieger C;Gläser S;González JR;Grallert H;Hammond CJ;Harris SE;Hartikainen AL;Heliövaara M;Henderson J;Hocking L;Horikoshi M;Hutri-Kähönen N;Ingelsson E;Johansson Å;Kemp JP;Kolcic I;Kumar A;Lind L;Melén E;Musk AW;Navarro P;Nickle DC;Padmanabhan S;Raitakari OT;Ried JS;Ripatti S;Schulz H;Scott RA;Sin DD;Starr JM;UK BiLEVE;Viñuela A;Völzke H;Wild SH;Wright AF;Zemunik T;Jarvis DL;Spector TD;Evans DM;Lehtimäki T;Vitart V;Kähönen M;Gyllensten U;Rudan I;Deary IJ;Karrasch S;Probst-Hensch NM;Heinrich J;Stubbe B;Wilson JF;Wareham NJ;James AL;Morris AP;Jarvelin MR;Hayward C;Sayers I;Strachan DP;Hall IP;Tobin MD
通讯作者：
Tobin MD
影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
影响因子：
3.1
作者：
Crowley, George;Kwon, Sophia;Nolan, Anna
通讯作者：
Nolan, Anna
DOI：
10.1083/jcb.201203065
发表时间：
2012-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kiyozumi D;Takeichi M;Nakano I;Sato Y;Fukuda T;Sekiguchi K
通讯作者：
Sekiguchi K
影响因子：
4.8
作者：
Morimura, N;Tezuka, Y;Tezuka, K
通讯作者：
Tezuka, K