Fgf10 deficiency is causative for lethality in a mouse model of bronchopulmonary dysplasia.
Fgf10 deficiency is causative for lethality in a mouse model of bronchopulmonary dysplasia.
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DOI：
10.1002/path.4834
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发表时间：
2017-01
影响因子：
7.3
通讯作者：
Bellusci, Saverio
中科院分区：
文献类型：
--
作者：
Chao, Cho-Ming;Yahya, Faady;Moiseenko, Alena;Tiozzo, Caterina;Shrestha, Amit;Ahmadvand, Negah;El Agha, Elie;Quantius, Jennifer;Dilai, Salma;Kheirollahi, Vahid;Jones, Matthew;Wilhem, Jochen;Carraro, Gianni;Ehrhardt, Harald;Zimmer, Klaus-Peter;Barreto, Guillermo;Ahlbrecht, Katrin;Morty, Rory E.;Herold, Susanne;Abellar, Rosanna G.;Seeger, Werner;Schermuly, Ralph;Zhang, Jin-San;Minoo, Parviz;Bellusci, Saverio
炎症诱导的FGF 10蛋白缺乏与支气管肺发育不良（BPD）相关，BPD是一种早产儿慢性肺部疾病，其特征是肺泡发育受阻。到目前为止，缺乏FGF 10在肺部疾病中直接作用的实验证据。使用高氧诱导的新生儿肺损伤作为BPD小鼠模型，研究了Fgf 10缺乏对Fgf 10 +/−与Fgf 10 +/+幼仔的影响。在常氧条件下，未观察到Fgf 10 +/+或Fgf 10 +/−幼仔的致死性。相比之下，所有Fgf 10 +/−幼仔在高氧损伤的8天内死亡，从第5天开始死亡，而Fgf 10 +/+幼仔都存活。在出生后第3天，在常氧或高氧暴露后，收集来自两种基因型的幼仔的肺用于进一步分析。在高氧时，Fgf 10 +/−肺表现出肺泡发育不良增加。在常氧条件下，Fgf 10 +/−组与对照组肺的FACS分析显示肺泡上皮II型（AECII）细胞与总Epcam阳性细胞的比例降低。此外，基因阵列分析表明，在来自Fgf 10 +/−肺的分离AECII细胞中，AECII减少，AECI转录组特征增加。这种分化不平衡也见于高氧症，并与成熟表面活性蛋白B和C表达减少有关。出生后在高氧环境下Fgfr 2b配体活性的减弱也会导致致死率增加，同时表面活性剂表达减少。总之，Fgf 10 mRNA水平降低导致先天性肺缺陷，这与出生后存活率相符，但损害了肺科普亚致死性高氧损伤的能力。Fgf 10缺乏影响AECII细胞形成的定量和定性。此外，Fgfr 2b配体对新生儿高氧暴露后的修复也很重要。AECII细胞缺陷可能是BPD患者的额外并发症。
Inflammation-induced FGF10 protein deficiency is associated with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely born infants characterized by arrested alveolar development. So far, experimental evidence for a direct role of FGF10 in lung disease is lacking. Using the hyperoxia-induced neonatal lung injury as a mouse model of BPD, the impact of Fgf10 deficiency in Fgf10+/− versus Fgf10+/+ pups was investigated. In normoxia, no lethality of Fgf10+/+ or Fgf10+/− pups was observed. By contrast, all Fgf10+/− pups died within 8 days of hyperoxic injury, with lethality starting at day 5, whereas Fgf10+/+ pups were all alive. Lungs of pups from the two genotypes were collected on postnatal day 3 following normoxia or hyperoxia exposure for further analysis. In hyperoxia, Fgf10+/− lungs exhibited increased hypoalveolarization. Analysis by FACS of the Fgf10+/− versus control lungs in normoxia, revealed a decreased ratio of alveolar epithelial type II (AECII) cells over total Epcam-positive cells. In addition, gene array analysis indicated reduced AECII and increased AECI transcriptome signatures in isolated AECII cells from Fgf10+/− lungs. Such an imbalance in differentiation is also seen in hyperoxia and associated with reduced mature surfactant protein B and C expression. Attenuation of the activity of Fgfr2b ligands post-natally in the context of hyperoxia lead also to increased lethality with decreased surfactant expression. In summary, decreased Fgf10 mRNA levels leads to congenital lung defects, which are compatible with postnatal survival, but which compromise the ability of the lungs to cope with sub-lethal hyperoxic injury. Fgf10 deficiency affects quantitatively and qualitatively the formation of AECII cells. In addition, Fgfr2b ligands are also important for repair after hyperoxia exposure in neonates. Deficient AECII cells could be an additional complication for patients with BPD.
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影响因子：
3.2
作者：
El Agha E;Bellusci S
通讯作者：
Bellusci S
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
8
作者：
Klinger, Gil;Levy, Itzhak;Reichman, Brian
通讯作者：
Reichman, Brian
影响因子：
3.7
作者：
Danopoulos S;Parsa S;Al Alam D;Tabatabai R;Baptista S;Tiozzo C;Carraro G;Wheeler M;Barreto G;Braun T;Li X;Hajihosseini MK;Bellusci S
通讯作者：
Bellusci S
DOI：
10.4049/jimmunol.1001857
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Benjamin JT;Carver BJ;Plosa EJ;Yamamoto Y;Miller JD;Liu JH;van der Meer R;Blackwell TS;Prince LS
通讯作者：
Prince LS