Macrophage-derived IGF-1 protects the neonatal intestine against necrotizing enterocolitis by promoting microvascular development.
Macrophage-derived IGF-1 protects the neonatal intestine against necrotizing enterocolitis by promoting microvascular development.
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巨噬细胞来源的IGF-1通过促进微血管发育来保护新生儿肠道免受坏死性小肠结肠炎的侵袭。
DOI：
10.1038/s42003-022-03252-9
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发表时间：
2022-04-06
影响因子：
5.9
通讯作者：
De Plaen IG
中科院分区：
文献类型：
--
作者：
Yan X;Managlia E;Zhao YY;Tan XD;De Plaen IG
坏死性小肠结肠炎（NEC）是早产儿的一种致死性肠道坏死性疾病。低水平的IGF-1使早产儿易患NEC。虽然越来越多的证据表明，有缺陷的围产期肠道微血管发育在NEC中发挥作用，所涉及的机制仍然不完全清楚。我们在这里报告，血清和肠道IGF-1的发育调节在围产期的小鼠和减少在实验NEC。新生儿肠道巨噬细胞产生IGF-1并通过IGF-1信号转导促进体外内皮细胞发芽。在体内，在新生儿肠道中，巨噬细胞衍生的IGF-1促进VEGF表达和内皮细胞增殖，并防止实验性NEC。外源性IGF-1保留肠道微血管密度，并防止实验性NEC。在人NEC组织中，绒毛内皮细胞增殖和产生IGF-1的巨噬细胞与对照组相比减少。总之，我们的研究结果表明，新生儿巨噬细胞产生的IGF-1缺陷会损害新生儿肠道微血管发育，并使肠道易患坏死性小肠结肠炎。这项研究强调了巨噬细胞衍生的IGF-1对新生儿肠道微血管发育的影响，以及对坏死性小肠结肠炎的保护作用。
Necrotizing enterocolitis (NEC) is a deadly bowel necrotic disease of premature infants. Low levels of plasma IGF-1 predispose premature infants to NEC. While increasing evidence suggests that defective perinatal intestinal microvascular development plays a role in NEC, the involved mechanism remains incompletely understood. We report here that serum and intestinal IGF-1 are developmentally regulated during the perinatal period in mice and decrease during experimental NEC. Neonatal intestinal macrophages produce IGF-1 and promote endothelial cell sprouting in vitro via IGF-1 signaling. In vivo, in the neonatal intestine, macrophage-derived IGF-1 promotes VEGF expression and endothelial cell proliferation and protects against experimental NEC. Exogenous IGF-1 preserves intestinal microvascular density and protects against experimental NEC. In human NEC tissues, villous endothelial cell proliferation and IGF-1- producing macrophages are decreased compared to controls. Together, our results suggest that defective IGF-1-production by neonatal macrophages impairs neonatal intestinal microvascular development and predisposes the intestine to necrotizing enterocolitis. This study highlights the impact of macrophage-derived IGF-1 on the microvascular development in the neonatal intestine and a resulting protective effect against necrotizing enterocolitis.
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影响因子：
9.8
作者：
Dallinga MG;Yetkin-Arik B;Kayser RP;Vogels IMC;Nowak-Sliwinska P;Griffioen AW;van Noorden CJF;Klaassen I;Schlingemann RO
通讯作者：
Schlingemann RO
影响因子：
3.6
作者：
Bowker RM;Yan X;Managlia E;Liu SXL;Marek C;Tan XD;De Plaen IG
通讯作者：
De Plaen IG
DOI：
10.1016/j.ghir.2017.11.006
发表时间：
2018-04
期刊：
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
影响因子：
--
作者：
Hellgren G;Löfqvist C;Hansen-Pupp I;Gram M;Smith LE;Ley D;Hellström A
通讯作者：
Hellström A
影响因子：
7.7
作者：
Imrie H;Viswambharan H;Sukumar P;Abbas A;Cubbon RM;Yuldasheva N;Gage M;Smith J;Galloway S;Skromna A;Rashid ST;Futers TS;Xuan S;Gatenby VK;Grant PJ;Channon KM;Beech DJ;Wheatcroft SB;Kearney MT
通讯作者：
Kearney MT
DOI：
10.1152/ajpgi.00317.2012
发表时间：
2013-01-01
影响因子：
4.5
作者：
Cherrington, Nathan J.;Estrada, Teresa E.;Halpern, Melissa D.
通讯作者：
Halpern, Melissa D.