RRC ID |
44330
|
著者 |
Tong L, Png E, Aihua H, Yong SS, Yeo HL, Riau A, Mendoz E, Chaurasia SS, Lim CT, Yiu TW, Iismaa SE.
|
タイトル |
Molecular mechanism of transglutaminase-2 in corneal epithelial migration and adhesion.
|
ジャーナル |
Biochim Biophys Acta
|
Abstract |
Migration of cells in the ocular surface underpins physiological wound healing as well as many human diseases. Transglutaminase (TG)-2 is a multifunctional cross-linking enzyme involved in the migration of skin fibroblasts and wound healing, however, its functional role in epithelial migration has not been evaluated. This study investigated the importance of TG-2 in a murine corneal wound healing model as well as the mechanistic role of TG-2 in the regulation of related biological processes such as cell adhesion and migration of cultured human corneal epithelial (HCE-T) cells. Corneal wound closure was delayed in homozygous TG-2 deleted mice compared to wild type mice. HCE-T cells that were knocked-down for TG-2 expression through stable expression of a short-hairpin (sh) RNA targeting TG-2, were delayed in closure of scratch wounds (48 compared to 12h in control cells expressing scrambled shRNA). TG-2 knockdown did not influence epithelial cell cycle progression or proliferation, rather, it led to reduced epithelial cell adhesion, spreading and velocity of migration. At the molecular level, TG-2 knockdown reduced phosphorylation of β-3 integrin at Tyr747, paxillin at Ser178, vinculin at Tyr822 and focal adhesion kinase at Tyr925 simultaneous with reduced activation of Rac and CDC42. Phosphorylation of paxillin at Ser178A has been shown to be indispensable for the migration of corneal epithelial cells (Kimura et al., 2008) [18]. TG-2 dependent β-3 integrin activation, serine-phosphorylation of paxillin, and Rac and CDC42 activation may thus play a key functional role in enhancing corneal epithelial cell adhesion and migration during wound healing.
|
巻・号 |
1833(6)
|
ページ |
1304-15
|
公開日 |
2013-6-1
|
DOI |
10.1016/j.bbamcr.2013.02.030
|
PII |
S0167-4889(13)00088-8
|
PMID |
23466867
|
MeSH |
Animals
Apoptosis
Blotting, Western
Cell Adhesion*
Cell Cycle
Cell Movement*
Cell Proliferation
Epithelium, Corneal / cytology*
Epithelium, Corneal / metabolism
Fluorescent Antibody Technique
GTP-Binding Proteins / antagonists & inhibitors
GTP-Binding Proteins / physiology*
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Glutamine gamma Glutamyltransferase 2
RNA, Small Interfering / genetics
Transglutaminases / antagonists & inhibitors
Transglutaminases / physiology*
Wound Healing / physiology*
|
IF |
3.411
|
引用数 |
13
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
HCE-T(RCB2280) |