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Query: UMLS:C0001511 (
Adhesion
)
5,955
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Wounding of skin activates epidermal cell migration over exposed dermal collagen and fibronectin and over
laminin 5
secreted into the provisional basement membrane. Gap junctional intercellular communication (GJIC) has been proposed to integrate the individual motile cells into a synchronized colony. We found that outgrowths of human keratinocytes in wounds or epibole cultures display parallel changes in the expression of
laminin 5
, integrin alpha3beta1, E-cadherin, and the gap junctional protein connexin 43.
Adhesion
of keratinocytes on
laminin 5
, collagen, and fibronectin was found to differentially regulate GJIC. When keratinocytes were adhered on
laminin 5
, both structural (assembly of connexin 43 in gap junctions) and functional (dye transfer) assays showed a two- to threefold increase compared with collagen and five- to eightfold over fibronectin. Based on studies with immobilized integrin antibody and integrin-transfected Chinese hamster ovary cells, the interaction of integrin alpha3beta1 with
laminin 5
was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking alpha3beta1-
laminin 5
interactions to GJIC indicated that protein trafficking and Rho signaling were both required. We suggest that adhesion of epithelial cells to
laminin 5
in the basement membrane via alpha3beta1 promotes GJIC that integrates individual cells into synchronized epiboles.
...
PMID:Cellular interaction of integrin alpha3beta1 with laminin 5 promotes gap junctional communication. 985 64
Adhesion
of keratinocytes in a wound outgrowth to
laminin 5
in the basement membrane via integrins alpha6beta4 and alpha3beta1 is distinct from adhesion to dermal collagen via alpha2beta1 or to fibronectin via alpha5beta1. Leading cells in the outgrowth are distinguished from following keratinocytes by deposition of
laminin 5
, failure to communicate via gap junctions and sensitivity to toxin B, an inhibitor of RhoGTPase. Laminin 5 deposited by leading keratinocytes onto dermal collagen dominates over dermal ligands and changes the cell signals required for adhesion from collagen-dependent to laminin-5-dependent. Thus, deposition of
laminin 5
can instruct keratinocytes to switch from an activated phenotype to a quiescent and integrated epithelial phenotype.
...
PMID:Deposition of laminin 5 in epidermal wounds regulates integrin signaling and adhesion. 1097 89
Wounding of the epidermis signals the transition of keratinocytes from quiescent anchorage on endogenous basement membrane
laminin 5
to migration on exposed dermal collagen. In this study, we attempt to characterize activation signals that transform quiescent keratinocytes into migratory leading cells at the wound edge. Previously, we reported that adhesion and spreading on collagen via integrin alpha(2)beta(1) by cultured human foreskin keratinocytes (HFKs) requires RhoGTP, a regulator of actin stress fibers. In contrast, adhesion and spreading on
laminin 5
requires integrins alpha(3)beta(1) and alpha(6)beta(4) and is dependent on phosphoinositide 3-hydroxykinase (Nguyen, B. P., Gil, S. G., and Carter, W. G. (2000) J. Biol. Chem. 275, 31896-31907). Here, we report that quiescent HFKs do not adhere to collagen but adhere and spread on
laminin 5
. By using collagen adhesion as one criterion for conversion to a "leading wound cell," we found that activation of collagen adhesion requires elevation of RhoGTP.
Adhesion
of quiescent HFKs to
laminin 5
via integrin alpha(3)beta(1) and alpha(6)beta(4) is sufficient to increase levels of RhoGTP required for adhesion and spreading on collagen. Consistently, adhesion of quiescent HFKs to
laminin 5
, but not collagen, also promotes expression of the precursor form of
laminin 5
, a characteristic of leading keratinocytes in the epidermal outgrowth. We suggest that wounding of quiescent epidermis initiates adhesion and spreading of keratinocytes at the wound edge on endogenous basement membrane
laminin 5
via alpha(3)beta(1) and alpha(6)beta(4) in a Rho-independent mechanism. Spreading on endogenous
laminin 5
via alpha(3)beta(1) is necessary but not sufficient to elevate expression of precursor
laminin 5
and RhoGTP, allowing for subsequent collagen adhesion via alpha(2)beta(1), all characteristics of leading keratinocytes in the epidermal outgrowth.
...
PMID:Ligation of integrin alpha 3beta 1 by laminin 5 at the wound edge activates Rho-dependent adhesion of leading keratinocytes on collagen. 1157 Dec 78
Quiescent epidermis anchors to
laminin 5
in the basement membrane via integrin alpha6beta4. Wounding elevates expression of
laminin 5
, generating leading keratinocytes (LKs) that migrate via beta1 integrins. Laminin 5 was evaluated as a regulator of cell signaling, and mRNA and protein expression in LKs. An in vitro wound model was developed based on suspension and re-adhesion of quiescent human keratinocytes (HKs). DNA microarrays identified multiple mRNAs elevated 1.5 hours after suspension and re-adhesion including activation transcription factor 3 (ATF3). In vitro and in vivo, levels of ATF3 protein elevate in nuclei of LKs, but not in nuclei of the following cells, 2 hours after suspension or wounding but decline by 12-18 hours post injury. Significantly, null defects in
laminin 5
or integrin beta4 that inhibit anchorage chronically elevate ATF3 in vivo. This suggests that adhesion to
laminin 5
, but not other ligands, suppresses activation. On suspension, ATF3 and other transcripts in the microarrays are elevated by phosphorylated p38 mitogen-activated protein kinase (P-p38), a stress kinase that regulates mRNA and cell motility. Inhibition of P-p38 with SB203580 prevents phosphorylation of ATF2, a transcription factor for ATF3 in LKs. Re-adhesion to
laminin 5
via alpha6beta4 dephosphorylates P-p38 and suppresses ATF3 protein relative to cells in suspension. Thus, wounding of quiescent HKs disrupts
laminin 5
adhesion to activate p38, generating mRNA transcripts that define LKs.
Adhesion
to deposits of
laminin 5
via alpha6beta4 suppresses P-p38 and activation mRNAs including ATF3. Defects in
laminin 5
and alpha6beta4 sustain P-p38 with probable pathological effects on transcription and migration.
...
PMID:Wounding activates p38 map kinase and activation transcription factor 3 in leading keratinocytes. 1607 89
In vivo in the prostate gland, basal epithelial cells adhere to
laminin 5
(LM5) via alpha3beta1 and alpha6beta4 integrins. When placed in culture primary prostate basal epithelial cells secrete and adhere to their own LM5-rich matrix.
Adhesion
to LM5 is required for cell survival that is dependent on integrin-mediated, ligand-independent activation of the epidermal growth factor receptor (EGFR) and the cytoplasmic tyrosine kinase Src, but not PI-3K. Integrin-mediated adhesion via alpha3beta1, but not alpha6beta4 integrin, supports cell survival through EGFR by signaling downstream to Erk. PC3 cells, which do not activate EGFR or Erk on LM5-rich matrices, are not dependent on this pathway for survival. PC3 cells are dependent on PI-3K for survival and undergo caspase-dependent death when PI-3K is inhibited. The death induced by inhibition of EGFR or Src in normal primary prostate cells is not mediated through or dependent on caspase activation, but depends on the induction of reactive oxygen species. In addition the presence of an autophagic pathway, maintained by adhesion to matrix through alpha3beta1 and alpha6beta4, prevents the induction of caspases when EGFR or Src is inhibited. Suppression of autophagy is sufficient to induce caspase activation and apoptosis in LM5-adherent primary prostate epithelial cells.
...
PMID:Inhibition of integrin-mediated crosstalk with epidermal growth factor receptor/Erk or Src signaling pathways in autophagic prostate epithelial cells induces caspase-independent death. 1747 74
Transplantation of retinal pigment epithelium (RPE) following removal of choroidal neovascular membranes has been attempted in patients with age-related macular degeneration (AMD). However, inability of transplanted RPE to initially attach and subsequently proliferate on Bruch's membrane may lead to failure of RPE transplants and poor visual outcomes. Integrin alpha(6)beta(4) functions as a receptor for laminin, the major component of Bruch's membrane, and mediates the stable attachment of most epithelial cells to the underlying basement membrane. To improve adhesion and proliferation of transplanted RPE on Bruch's membrane, we elucidated the roles of integrin alpha(6)beta(4) in RPE adhesion to extracellular matrix and investigated whether ex vivo gene transfer of integrin alpha(6) and beta(4) in RPE could promote adhesion and proliferation of transplanted RPE on Bruch's membrane. The expression of integrin alpha(6) and beta(4) mRNA and surface protein in ARPE-19 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. We generated point mutation in the ligand binding domain of integrin alpha(6) and beta(4) by using site-directed mutagenesis and transfected these mutated constructs into ARPE-19 cells.
Adhesion
assay was used to determine the roles of integrin alpha(6) and beta(4) in RPE adhesion to extracellular matrix. In addition, we transfected full-length alpha(6) cDNA or beta(4) cDNA into ARPE-19 cells. The reattachment and proliferation ratios of alpha(6)-cDNA- or beta(4)-cDNA-transfected ARPE-19 cells on different layers of Bruch's membrane were determined by cell adhesion and proliferation assays. Cell morphology and surface coverage were evaluated by scanning electron microscopy 7 days after plating on various layers of Bruch's membrane. We found that integrin alpha(6) and beta(4) mRNA and proteins were constitutively expressed in ARPE-19 cells. Decreased endogenous integrin alpha(6) and beta(4) expression by selective mutation of amino acid residues caused a significant reduction in adhesion of ARPE-19 cells to
laminin 5
. Modification of integrin expression by transfection of alpha(6) cDNA into ARPE-19 cells induced a significant increase in cell adhesion to
laminin 5
, fibronectin, whereas transfection with beta(4) cDNA caused increased adhesion only to
laminin 5
. alpha(6)-cDNA-transfectants increased cell attachment and proliferation on all layers of Bruch's membrane, whereas beta(4)-cDNA-transfectants enhanced adhesion and proliferation on basal lamina and inner collagenous layers. These data indicate that integrin alpha(6) and beta(4) play a role in adhesion of ARPE-19 cells to extracellular matrix. Modification of integrin expression by ex vivo genetic manipulation in RPE might be an alternative strategy to increase the success of RPE transplantation.
...
PMID:Overexpression of integrin alpha6 and beta4 enhances adhesion and proliferation of human retinal pigment epithelial cells on layers of porcine Bruch's membrane. 1895 47
