Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats
Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats
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DOI：
10.1152/ajpgi.2000.279.5.g1011
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发表时间：
2000-11-01
影响因子：
4.5
通讯作者：
Sartor, RB
中科院分区：
文献类型：
--
作者：
Han, DS;Li, FL;Sartor, RB
角质形成细胞生长因子-2(KGF-2，repifermin)是KGF-1的同系物，具有上皮细胞有丝分裂活性。我们研究了KGF-2在肠溃疡中的治疗作用及其保护机制。在预防和治疗方案中，KGF-2(0.3-5 mg/kg)在吲哚美辛(Indo)诱导的小鼠小肠溃疡之前或之后给予。在急性研究中，在INDO前注射KGF-2长达7天，或在INDO后每天注射KGF-2 5天。在一项为期15天的慢性研究中，从INDO前或INDO后7天开始，每天静脉注射KGF-2。通过盲法肉眼和显微镜下炎症评分、上皮BrdU染色、组织IL-1β、PGE(2)和羟脯氨酸浓度以及I型胶原RNA表达来评价损伤程度。通过上皮细胞增殖、损伤单层修复、PGE(2)分泌、COX-2和胶原mRNA的表达来评价KGF-2的体外作用。静脉注射KGF-2各指标均可明显减轻急性肠损伤，显著减少慢性溃疡。治疗前、每日输液、延迟治疗均有效。KGF-2可促进体外培养上皮细胞的修复，但对上皮细胞的增殖作用不大，可刺激培养上皮细胞COX-2的表达，并上调体内和体外PGE(2)的生成。KGF-2诱导培养的肠肌成纤维细胞表达胶原，但对体内纤维化无影响。这些结果表明，KGF-2通过刺激上皮修复和保护PG来抑制肠道炎症。
Keratinocyte growth factor-2 (KGF-2, repifermin) is a homolog of KGF-1 with epithelial mitogenic activities. We investigated the therapeutic role of KGF-2 in intestinal ulceration and its mechanisms of protection. KGF-2 (0.3-5 mg/kg) was administered before or after induction of small intestinal ulceration by indomethacin (Indo) in prevention and treatment protocols. In acute studies, KGF-2 was injected for up to 7 days before or daily for 5 days after Indo. In a 15-day chronic study, KGF-2 was injected intravenously daily beginning before or 7 days after Indo. Injury was evaluated by blinded macroscopic and microscopic inflammatory scores, epithelial BrdU staining, tissue IL-1 beta, PGE(2), and hydroxyproline concentrations, and collagen type I RNA expression. In vitro effects of KGF-2 were evaluated by epithelial cellular proliferation, restitution of wounded monolayers, PGE(2) secretion, and expression of COX-2 and collagen mRNA. Intravenous KGF-2 significantly decreased acute intestinal injury by all parameters and significantly decreased chronic ulceration. Pretreatment, daily infusion, and delayed treatment were effective. KGF-2 promoted in vitro epithelial restitution with only modest effects on epithelial cell proliferation, stimulated COX-2 expression in cultured epithelial cells, and upregulated in vitro and in vivo PGE(2) production. KGF-2 did not affect in vivo fibrosis, although it induced collagen expression in cultured intestinal myofibroblasts. These results suggest that KGF-2 inhibits intestinal inflammation by stimulating epithelial restitution and protective PGs.