Transcriptomic analyses reveal proinflammatory activation of human brain microvascular endothelial cells by aging-associated peptide medin and reversal by nanoliposomes.
Transcriptomic analyses reveal proinflammatory activation of human brain microvascular endothelial cells by aging-associated peptide medin and reversal by nanoliposomes.
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DOI：
10.1038/s41598-023-45959-7
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发表时间：
2023-11-01
影响因子：
4.6
通讯作者：
Migrino, Raymond Q.
中科院分区：
文献类型：
--
作者：
Zhang, Yining;Karamanova, Nina;Morrow, Kaleb T.;Madine, Jillian;Truran, Seth;Lozoya, Maria;Weissig, Volkmar;Li, Ming;Nikkhah, Mehdi;Park, Jin G.;Migrino, Raymond Q.
Medin是一种常见的血管淀粉样蛋白，近年来发现与阿尔茨海默病（AD）和血管性痴呆有关，其病理机制尚不清楚。我们的目的是确定暴露于medin的人脑微血管内皮细胞（HBMVECs）中转录组学特征和途径的变化，将其与暴露于β-淀粉样蛋白（Aβ）进行比较，并评估含单唾液酸神经节苷脂纳米脂质体（NL）的保护作用。HBMVEC暴露于medin（5 µM）20 h，不含或含Aβ（1-42）（2 µM）或NL（300 µg/mL），并进行RNA-seq和信号通路分析。另外，在用medin（5 µM）处理的HBMVEC中对选定的已鉴定基因进行逆转录聚合酶链反应，其中medin不含或含有NFκB抑制剂RO 106 -9920（10 µM）或NL（300 µg/mL）。Medin引起促炎基因上调，Aβ42联合治疗未加重，但NL逆转。差异表达基因的通路分析显示，多种促炎信号通路，如肿瘤坏死因子（TNF）和核因子-κB（NF κ B）信号通路，受到medin治疗的特异性影响。RO 106 -9920和NL减少了medin诱导的促炎活化。Medin部分通过NFκB诱导内皮细胞的促炎信号传导，而NL可逆转该信号传导。这可能对血管性衰老、AD和血管性痴呆的发病机制和治疗具有潜在意义。
Medin is a common vascular amyloidogenic peptide recently implicated in Alzheimer’s disease (AD) and vascular dementia and its pathology remains unknown. We aim to identify changes in transcriptomic profiles and pathways in human brain microvascular endothelial cells (HBMVECs) exposed to medin, compare that to exposure to β-amyloid (Aβ) and evaluate protection by monosialoganglioside-containing nanoliposomes (NL). HBMVECs were exposed for 20 h to medin (5 µM) without or with Aβ(1-42) (2 µM) or NL (300 µg/mL), and RNA-seq with signaling pathway analyses were performed. Separately, reverse transcription polymerase chain reaction of select identified genes was done in HBMVECs treated with medin (5 µM) without or with NFκB inhibitor RO106-9920 (10 µM) or NL (300 µg/mL). Medin caused upregulation of pro-inflammatory genes that was not aggravated by Aβ42 co-treatment but reversed by NL. Pathway analysis on differentially expressed genes revealed multiple pro-inflammatory signaling pathways, such as the tumor necrosis factor (TNF) and the nuclear factor-κB (NFkB) signaling pathways, were affected specifically by medin treatment. RO106-9920 and NL reduced medin-induced pro-inflammatory activation. Medin induced endothelial cell pro-inflammatory signaling in part via NFκB that was reversed by NL. This could have potential implications in the pathogenesis and treatment of vascular aging, AD and vascular dementia.
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影响因子：
15.1
作者：
Dietrich HH;Xiang C;Han BH;Zipfel GJ;Holtzman DM
通讯作者：
Holtzman DM
祖细胞和成熟人类星形胶质细胞的纯化和表征揭示了小鼠的转录和功能差异。
影响因子：
16.2
作者：
Zhang Y;Sloan SA;Clarke LE;Caneda C;Plaza CA;Blumenthal PD;Vogel H;Steinberg GK;Edwards MS;Li G;Duncan JA 3rd;Cheshier SH;Shuer LM;Chang EF;Grant GA;Gephart MG;Barres BA
通讯作者：
Barres BA
影响因子：
64.8
作者：
Wagner, Jessica;Degenhardt, Karoline;Veit, Marleen;Louros, Nikolaos;Konstantoulea, Katerina;Skodras, Angelos;Wild, Katleen;Liu, Ping;Obermueller, Ulrike;Bansal, Vikas;Dalmia, Anupriya;Haesler, Lisa M.;Lambert, Marius;De Vleeschouwer, Matthias;Davies, Hannah A.;Madine, Jillian;Kronenberg-Versteeg, Deborah;Feederle, Regina;Del Turco, Domenico;Nilsson, K. Peter R.;Lashley, Tammaryn;Deller, Thomas;Gearing, Marla;Walker, Lary C.;Heutink, Peter;Rousseau, Frederic;Schymkowitz, Joost;Jucker, Mathias;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
5.4
作者：
Franco DA;Truran S;Weissig V;Guzman-Villanueva D;Karamanova N;Senapati S;Burciu C;Ramirez-Alvarado M;Blancas-Mejia LM;Lindsay S;Hari P;Migrino RQ
通讯作者：
Migrino RQ
影响因子：
1.7
作者：
Kechin, Andrey;Boyarskikh, Uljana;Filipenko, Maxim
通讯作者：
Filipenko, Maxim