The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization.
The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization.
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DOI：
10.3389/fnmol.2020.605918
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发表时间：
2020
影响因子：
4.8
通讯作者：
DeAngelis MM
中科院分区：
文献类型：
--
作者：
Owen LA;Shirer K;Collazo SA;Szczotka K;Baker S;Wood B;Carroll L;Haaland B;Iwata T;Katikaneni LD;DeAngelis MM
早产儿视网膜病变（ROP）是早产儿视网膜血管成熟的致盲异常。尽管早产后延迟发病是治疗干预的窗口期，但我们无法预防或治愈ROP失明。一种自然形式的ROP保护存在于早发性先兆子痫的环境中，尽管没有很好地表征。由于缺血是ROP和先兆子痫的中心特征，我们假设血管生成介质可能是这种保护的基础。为了验证我们的假设，我们分析了在子痫前期和ROP病理生理中可能起作用的候选蛋白（HTRA-1、IGF-1、tgf - β-1和VEGF-A）的外周血表达。在一项包含40对母婴的发现队列分析中发现，HTRA-1（高温要求- a丝氨酸肽酶-1）升高与ROP风险增加和子痫前期缺失显著相关，因此符合子痫前期介导的ROP保护模型。我们验证了这些发现，并进一步证明了系统性婴儿HTRA-1表达与ROP发展风险之间的剂量反应，该验证队列由来自两个机构的早产儿组成。氧诱导视网膜病变（OIR）小鼠ROP模型的功能分析支持了我们在局部组织水平上的系统性人类发现，通过RT-PCR显示，在ROP疾病状态下，hta -1在神经感觉视网膜和视网膜色素上皮中的表达均升高。最后，过表达hta -1的转基因小鼠在该模型中表现出更大的ROP疾病严重程度。因此，HTRA-1可能是子痫前期ROP保护的基础，是目前尚不存在的一种疾病预防途径。
Retinopathy of prematurity (ROP) is a blinding aberrancy of retinal vascular maturation in preterm infants. Despite delayed onset after preterm birth, representing a window for therapeutic intervention, we cannot prevent or cure ROP blindness. A natural form of ROP protection exists in the setting of early-onset maternal preeclampsia, though is not well characterized. As ischemia is a central feature in both ROP and preeclampsia, we hypothesized that angiogenesis mediators may underlie this protection. To test our hypothesis we analyzed peripheral blood expression of candidate proteins with suggested roles in preeclamptic and ROP pathophysiology and with a proposed angiogenesis function (HTRA-1, IGF-1, TGFβ-1, and VEGF-A). Analysis in a discovery cohort of 40 maternal-infant pairs found that elevated HTRA-1 (high-temperature requirement-A serine peptidase-1) was significantly associated with increased risk of ROP and the absence of preeclampsia, thus fitting a model of preeclampsia-mediated ROP protection. We validated these findings and further demonstrated a dose-response between systemic infant HTRA-1 expression and risk for ROP development in a larger and more diverse validation cohort consisting of preterm infants recruited from two institutions. Functional analysis in the oxygen-induced retinopathy (OIR) murine model of ROP supported our systemic human findings at the local tissue level, demonstrating that HtrA-1 expression is elevated in both the neurosensory retina and retinal pigment epithelium by RT-PCR in the ROP disease state. Finally, transgenic mice over-expressing HtrA-1 demonstrate greater ROP disease severity in this model. Thus, HTRA-1 may underlie ROP protection in preeclampsia and represent an avenue for disease prevention, which does not currently exist.
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影响因子：
5.6
作者：
Ferrari, Giovanni;Cook, Brandoch D.;Terushkin, Vitaly;Pintucci, Giuseppe;Mignatti, Paolo
通讯作者：
Mignatti, Paolo
DOI：
10.1056/nejmoa0911781
发表时间：
2010-05-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network;Carlo WA;Finer NN;Walsh MC;Rich W;Gantz MG;Laptook AR;Yoder BA;Faix RG;Das A;Poole WK;Schibler K;Newman NS;Ambalavanan N;Frantz ID 3rd;Piazza AJ;Sánchez PJ;Morris BH;Laroia N;Phelps DL;Poindexter BB;Cotten CM;Van Meurs KP;Duara S;Narendran V;Sood BG;O'Shea TM;Bell EF;Ehrenkranz RA;Watterberg KL;Higgins RD
通讯作者：
Higgins RD
PTB 相关剪接因子抑制氧诱导视网膜病变小鼠模型中 IGF-1 诱导的 VEGF 上调
影响因子：
3.6
作者：
Dong, Lijie;Nian, Hong;Li, Xiaorong
通讯作者：
Li, Xiaorong
影响因子：
8.1
作者：
Daniel, Ebenezer;Quinn, Graham E.;Ying, Gui-Shuang
通讯作者：
Ying, Gui-Shuang
影响因子：
6.8
作者：
Bankowski, E;Palka, J;Jaworski, S
通讯作者：
Jaworski, S