Premium
EXOGENOUS PHOSPHOLIPASE C STIMULATES EPITHELIAL CELL MIGRATION AND INTEGRIN EXPRESSION IN VITRO
Author(s) -
Firth James D,
Putnins Edward E,
Larjava Hannu,
Uitto VeliJukka
Publication year - 2001
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.2001.00086.x
Subject(s) - fibronectin , phospholipase c , microbiology and biotechnology , integrin , cell migration , biology , phospholipase , focal adhesion , signal transduction , vitronectin , phospholipase d , cell , extracellular matrix , biochemistry , enzyme
Phospholipase C secreted by bacterial pathogens has been identified as a virulence factor in several human diseases and has been implicated in impeding wound healing. The role of phospholipase C in the intracellular signal control of epithelial growth was studied in normal human skin keratinocytes cultured in conditions simulating aspects of wound healing. Bacillus cereus phospholipase C decreased cell‐cell contact and increased cell migration resulting in disruption of the advancing epithelial sheet. Phospholipase C‐induced migration was blocked by inhibitor of the phosphoinositol signal transduction pathway neomycin sulfate and protein kinase C inhibitor RO‐31–8220. Induced migration was associated with elevated levels of matrix metalloproteinase‐9 which, when blocked by tissue inhibitor of metalloproteinase‐1, was accompanied by a loss of migration. Adhesion studies showed that phospholipase C treatment enhanced cell binding to fibronectin, vitronectin and collagen IV. Immunostained phospholipase C‐stimulated cells cultured on fibronectin showed enhanced expression and relocation of the integrin subunits α v , α 5 and β 1 . Confocal microscopy showed that phospholipase C‐induced levels of integrin subunit β 1 were predominantly deposited on the basal surface of the cell apparently in focal contacts and associated with actin stress fibers. These results indicate that exogenous phospholipase C signaling from a bacterial source may play an important role in perturbing normal reepithelialization via altered expression of integrins and matrix metalloproteinase‐9.