Reduced NGF in Gastric Endothelial Cells Is One of the Main Causes of Impaired Angiogenesis in Aging Gastric Mucosa.
Reduced NGF in Gastric Endothelial Cells Is One of the Main Causes of Impaired Angiogenesis in Aging Gastric Mucosa.
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DOI：
10.1016/j.jcmgh.2018.05.003
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发表时间：
2018
影响因子：
7.2
通讯作者：
Tarnawski AS
中科院分区：
文献类型：
--
作者：
Ahluwalia A;Jones MK;Hoa N;Zhu E;Brzozowski T;Tarnawski AS
衰老的胃黏膜由于血管生成受损而增加了对损伤和延迟愈合的易感性，但其机制尚不完全清楚。我们研究了老化胃粘膜血管生成的损伤是否由胃内皮细胞（ECs）中神经生长因子（NGF）的缺乏引起，以及NGF治疗是否可以逆转这种损伤。在年轻和衰老大鼠胃粘膜内皮细胞（GECs）中，我们检测了：(1)体外血管生成，(2)NGF表达，(3)NGF处理对血管生成、GEC增殖和迁移的影响，以及对血清反应因子的依赖。在年轻和衰老大鼠的体内研究中，我们检测了NGF在胃粘膜中的表达以及NGF治疗对血管生成和胃溃疡愈合的影响。为了确定人类的相关性，我们检测了衰老（≥70岁）和年轻（≤40岁）个体胃粘膜活检标本中NGF的表达。在培养的衰老gec中，NGF的表达和血管生成与年轻gec相比显著降低了3.0倍和4.1倍。NGF治疗逆转了衰老gec血管生成损伤，而血清反应因子沉默完全消除了这种反应。在衰老大鼠胃粘膜中，NGF在GECs中的表达明显低于年轻大鼠。在衰老大鼠中，局部NGF治疗显著增加血管生成并加速胃溃疡愈合。在衰老的人类受试者中，胃粘膜血管内皮细胞中NGF的表达比年轻人减少了5.5倍。内皮细胞中NGF缺乏是衰老胃粘膜血管生成受损和溃疡延迟愈合的关键机制。局部NGF治疗可以逆转这些损伤。
Aging gastric mucosa has increased susceptibility to injury and delayed healing owing to impaired angiogenesis, but the mechanisms are not fully known. We examined whether impairment of angiogenesis in aging gastric mucosa is caused by deficiency of nerve growth factor (NGF) in gastric endothelial cells (ECs), and whether NGF therapy could reverse this impairment. In gastric mucosal ECs (GECs) isolated from young and aging rats we examined the following: (1) in vitro angiogenesis, (2) NGF expression, and (3) the effect of NGF treatment on angiogenesis, GEC proliferation and migration, and dependence on serum response factor. In in vivo studies in young and aging rats, we examined NGF expression in gastric mucosa and the effect of NGF treatment on angiogenesis and gastric ulcer healing. To determine human relevance, we examined NGF expression in gastric mucosal biopsy specimens of aging (≥70 y) and young (≤40 y) individuals. In cultured aging GECs, NGF expression and angiogenesis were reduced significantly by 3.0-fold and 4.1-fold vs young GECs. NGF therapy reversed impairment of angiogenesis in aging GECs, and serum response factor silencing completely abolished this response. In gastric mucosa of aging rats, NGF expression in GECs was reduced significantly vs young rats. In aging rats, local NGF treatment significantly increased angiogenesis and accelerated gastric ulcer healing. In aging human subjects, NGF expression in ECs of gastric mucosal vessels was 5.5-fold reduced vs young individuals. NGF deficiency in ECs is a key mechanism underlying impaired angiogenesis and delayed ulcer healing in aging gastric mucosa. Local NGF therapy can reverse these impairments.
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影响因子：
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作者：
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