| RRC ID |
58624
|
| 著者 |
Konno T, Kohno T, Kikuchi S, Shimada H, Satohisa S, Saito T, Kondoh M, Kojima T.
|
| タイトル |
Epithelial barrier dysfunction and cell migration induction via JNK/cofilin/actin by angubindin-1.
|
| ジャーナル |
Tissue Barriers
|
| Abstract |
Angulin-1/LSR is a tricellular tight junction molecule, that plays an important role in maintaining the epithelial and endothelial barriers. The actin cytoskeleton at tricellular contacts also contributes to the maintenance of the epithelial barrier. Loss of angulin-1/LSR enhances the migration of various cancer cells. Angubindin-1 is a novel binder to angulin-1/LSR and angulin-3. It is a peptide generated from the angulin-1 binding site of Clostridium perfringens iota toxin, which affects the actin cytoskeleton and decreases the epithelial and endothelial barrier functions. However, its regulatory mechanisms are not well understood. To investigate the regulatory mechanisms of the epithelial barrier dysfunction and cell migration induction by angubindin-1, we used human endometrial cancer cell line Sawano, which has high LSR expression and the epithelial barrier function. Angubindin-1 decreased LSR expression and the epithelial barrier function and increased cell migration. It inhibited the recovery of the epithelial barrier function in a Ca-switch model. At tricellular contacts, sinking of the membrane and an increase of actin fibers near the junctions were caused by angubindin-1. It dynamically changed F-actin from lines to dot-like structures at tricellular contacts. Angubindin-1 transiently increased the phosphorylation of cofilin and JNK, which are involved in the regulation of the intracellular actin cytoskeleton. Furthermore, knockdown of JNK and the JNK inhibitor SP600125 prevented the decrease of the epithelial barrier function and the increase of cell migration induced by angubindin-1. These findings suggest that angubindin-1 might reversibly regulate the epithelial barrier and cell migration at tricellular contacts via JNK/cofilin/actin cytoskeleton dynamics.
|
| 巻・号 |
8(1)
|
| ページ |
1695475
|
| 公開日 |
2020-1-1
|
| DOI |
10.1080/21688370.2019.1695475
|
| PMID |
31782346
|
| PMC |
PMC7063864
|
| MeSH |
Bacterial Toxins / pharmacology
Bacterial Toxins / therapeutic use*
Cell Movement
Epithelial Cells / metabolism*
Humans
MAP Kinase Kinase 4 / metabolism*
Tight Junctions / metabolism*
|
| リソース情報 |
| ヒト・動物細胞 |
Sawano(RCB1152) |
