Molecular mechanism of transglutaminase-2 in corneal epithelial migration and adhesion

被引：23

作者：

Tong, Louis ^{[1
,2
,3
,4
]}

Png, Evelyn ^{[1
]}

AiHua, Hou ^{[1
]}

Yong, Siew Sian ^{[1
]}

Yeo, Hui Ling ^{[1
]}

Riau, Andri ^{[1
]}

Mendoz, Earnest ^{[5
]}

Chaurasia, Shyam S. ^{[1
,4
,5
]}

Lim, Chwee Teck ^{[6
,7
]}

Yiu, Ting Wai ^{[8
]}

Iismaa, Siiri E. ^{[8
]}

机构：

[1] Singapore Eye Res Inst, Ocular Surface Res Grp, Singapore 168751, Singapore

[2] Singapore Natl Eye Ctr, Dept Cornea & External Eye Dis, Singapore 168751, Singapore

[3] Duke NUS Grad Med Sch, Off Clin Sci, Singapore, Singapore

[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore

[5] Duke NUS Grad Med Sch, SRP Neurosci & Behav Disorders, Singapore, Singapore

[6] Natl Univ Singapore, Div Bioengn, Singapore 117576, Singapore

[7] Natl Univ Singapore, Dept Mech Engn, Singapore 117576, Singapore

[8] Victor Chang Cardiac Res Inst, Mol Cardiol Program, Darlinghurst, NSW 2010, Australia

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2013年 / 1833卷 / 06期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

Migration; Adhesion; Transglutaminase; Cornea; Epithelium; Wound healing; SURFACE TISSUE TRANSGLUTAMINASE; CELL-ADHESION; TYROSINE PHOSPHORYLATION; CROSS-LINKING; FIBRONECTIN; EXPRESSION; LAMELLIPODIA; GTPASES; SERINE; CDC42;

D O I：

10.1016/j.bbamcr.2013.02.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 12 h 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 beta-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 beta-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. (c) 2013 Elsevier B.V. All rights reserved.

引用

页码：1304 / 1315

页数：12

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