Dragon's Blood Regulates Rac1-WAVE2-Arp2/3 Signaling Pathway to Protect Rat Intestinal Epithelial Barrier Dysfunction Induced by Simulated Microgravity.
Dragon's Blood Regulates Rac1-WAVE2-Arp2/3 Signaling Pathway to Protect Rat Intestinal Epithelial Barrier Dysfunction Induced by Simulated Microgravity.
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DOI：
10.3390/ijms22052722
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发表时间：
2021-03-08
影响因子：
5.6
通讯作者：
Deng Y
中科院分区：
文献类型：
--
作者：
Li Y;Liu S;Liu H;Cui Y;Deng Y
龙血是龙血竭(Dracaena cochinensis(Lour.)S.C.Chen(云南，中国)。作为一种传统中草药，它对肠道疾病具有保护作用。微重力可改变肠道内环境平衡。然而，在微重力条件下预防肠上皮屏障(IEB)功能障碍的潜在草药是不可用的。本研究旨在观察龙血对微重力所致IEB损伤的影响，并探讨其可能的作用机制。采用大鼠尾悬吊模型模拟微重力(SMG)。观察SMG大鼠空肠、回肠、结肠的组织形态、超微结构、通透性及连接蛋白的表达。用蛋白质组学方法鉴定DB对大鼠回肠黏膜的差异表达蛋白(DEPS)。Western blotting验证了DB保护IEB功能障碍的可能机制。在SMG处理的Caco-2细胞中，评价了DB中的几种成分的作用。DB通过修复微绒毛和隐窝，抑制炎症因子，降低通透性，上调SMG大鼠回肠紧密连接蛋白和黏附连接蛋白的表达，对IEB损伤具有保护作用。蛋白质组学分析表明，DB对大鼠回肠粘膜中的1080个DEPS有调节作用。DEPS在细胞-细胞黏附、焦点黏附和细胞骨架调节方面有显著的注解。DB可增加Rac1-WAVE2-Arp2/3通路蛋白的表达，增加F-肌动蛋白与G-肌动蛋白的比值，促进局灶性粘连的形成。丹参中的龙血素C对SMG处理的Caco-2细胞上皮屏障损伤有保护作用。DB对SMG诱导的肠上皮细胞功能障碍具有保护作用，其机制可能与通过rac1-WAVE2-Arp2/3途径形成局灶性黏附，促进肠上皮细胞迁移和屏障修复有关。
Dragon’s Blood is a red resin from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has shown protective effects on intestinal disorders. Microgravity could alter intestinal homeostasis. However, the potential herbal drugs for preventing intestine epithelial barrier (IEB) dysfunction under microgravity are not available. This study aimed to investigate the effects of Dragon’s Blood (DB) on microgravity-induced IEB injury and explore its underlying mechanism. A rat tail-suspension model was used to simulate microgravity (SMG). Histomorphology, ultrastructure, permeability, and expression of junction proteins in jejunum, ileum, and colon of SMG rats were determined. Proteomic analysis was used to identify differentially expressed proteins (DEPs) in rat ileum mucosa altered by DB. The potential mechanism of DB to protect IEB dysfunction was validated by western blotting. The effects of several components in DB were evaluated in SMG-treated Caco-2 cells. DB protected against IEB disruption by repairing microvilli and crypts, inhibiting inflammatory factors, lowering the permeability and upregulating the expression of tight and adherens junction proteins in the ileum of SMG rats. Proteomic analysis showed that DB regulated 1080 DEPs in rat ileum mucosa. DEPs were significantly annotated in cell–cell adhesion, focal adhesion, and cytoskeleton regulation. DB increased the expression of Rac1-WAVE2-Arp2/3 pathway proteins and F-actin to G-actin ratio, which promoted the formation of focal adhesions. Loureirin C in DB showed a protective effect on epithelial barrier injury in SMG-treated Caco-2 cells. DB could protect against IEB dysfunction induced by SMG, and its mechanism is associated with the formation of focal adhesions mediated by the Rac1-WAVE2-Arp2/3 pathway, which benefits intestinal epithelial cell migration and barrier repair.
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DOI：
10.3390/molecules190710650
发表时间：
2014-07-22
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Fan JY;Yi T;Sze-To CM;Zhu L;Peng WL;Zhang YZ;Zhao ZZ;Chen HB
通讯作者：
Chen HB
影响因子：
3.7
作者：
Burridge K;Guilluy C
通讯作者：
Guilluy C
影响因子：
4.6
作者：
Carvalho, Diego;Paulino, Margot;Abin-Carriquiry, Juan A.
通讯作者：
Abin-Carriquiry, Juan A.
影响因子：
3.4
作者：
La Barbera, Giorgia;Capriotti, Anna Laura;Lagana, Aldo
通讯作者：
Lagana, Aldo
影响因子：
4
作者：
Demontis GC;Germani MM;Caiani EG;Barravecchia I;Passino C;Angeloni D
通讯作者：
Angeloni D