Hemidesmosomes and anchoring fibril collagen appear synchronously during development and wound healing

Gipson, Ilene K.; Spurr-Michaud, Sandra; Tisdale, Ann

doi:10.1016/0012-1606(88)90136-4

Cited by 89 publications

(37 citation statements)

References 23 publications

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“…Epiligrin serves as a good candidate for a ligand for a614 in migrating keratinocytes. Hemidesomosomes could then form at the sites where anchoring filaments and anchoring fibers are formed (64)(65)(66). The a614 was often seen in several cell layers in the wound epithelium and not restricted to the basal surface of keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Expression of integrins and basement membrane components by wound keratinocytes.

Larjava¹,

Salo²,

Haapasalmi³

et al. 1993

J. Clin. Invest.

367

309

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Extracellular matrix proteins and their cellular receptors, integrins, play a fundamental role in keratinocyte adhesion and migration. During wound healing, keratinocytes detach, migrate until the two epithelial sheets confront, and then regenerate the basement membrane. We examined the expression of different integrins and their putative ligands in keratinocytes during human mucosal wound healing. Migrating keratinocytes continuously expressed kalinin but not the other typical components of the basement membrane zone: type IV collagen, laminin, and type VII collagen. When the epithelial sheets confronted each other, these missing basement membrane components started to appear gradually through the entire wound area. The expression of integrin 81 subunit was increased in keratinocytes during migration. The #,B-associated a2 and a3 subunits were expressed constantly by wound keratinocytes whereas the a5 subunit was present only in keratinocytes during reepithelialization. Furthermore, migrating cells started to express a,-integrins which were not present in the nonaffected epithelium. All keratinocytes also expressed the a684 integrin during migration. In the migrating cells, the distribution of integrins was altered. In normal mucosa, ,61-integrins were located mainly on the lateral plasma membrane and aQ84 at the basal surface of basal keratinocytes in the nonaffected tissue. In wounds, integrins were found in filopodia of migrating keratinocytes, and also surrounding cells in several cell layers of the migrating sheet. The results indicate that migrating keratinocytes in deep human wounds enlarge their integrin repertoire. The changes in integrin expression take place concomitantly with changes in the basement membrane composition, suggesting a close interplay of these two groups of molecules during wound healing. (J. Clin. Invest. 1993. 92:1425-1435

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Section: Discussionmentioning

confidence: 99%

Expression of integrins and basement membrane components by wound keratinocytes.

Larjava¹,

Salo²,

Haapasalmi³

et al. 1993

J. Clin. Invest.

367

309

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“…1A). The basal cells have hemidesmosomes at their basal aspect along their basement membrane (21). Both a6 and (4 localize to this area in mouse cornea by immunofluorescence microscopy ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes.

Stepp

Spurr-Michaud

Tisdale

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

445

254

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Antisera that recognize the a6 and (34 subunits of integrins were found by immunoelectron microscopy to localize to hemidesmosomes in the basal cells of mouse corneal epithelium. Immunoprecipitation experiments using extracts of metabolically labeled corneal epithelial cells indicate that the primary a6-subunit-containing integrin heterodimer present is a434 and not a6431. Here we extend previous studies to report that by immunofluorescence microscopy the a6 integrin subunit colocalizes with bullous pemphigoid antigen and type V1I collagen in newly forming hemidesmosomes in the developing 17-day fetal rabbit eye. Neither the composition of the anchoring filaments, which span the region between the hemidesmosomal plaque and the lamina densa of basement membrane where the globular domain of type VII collagen is located, nor the extracellular ligand of a6.84 is known. Once anchoring filament proteins are identified, it will be of interest to determine whether any bind to a484.Hemidesmosomes are cell-substrate adhesionjunctions present along the basal cell-basement membrane junction of stratified squamous epithelia (1,2). By comparison to desmosomes, biochemical characterization of the basic components of the hemidesmosome has been slow, due in part to difficulty in obtaining hemidesmosome-enriched cellular fractions. The only characterized component of the hemidesmosome is the bullous pemphigoid antigen (BPA), a 230-kDa protein present in the cytoplasmic plaque of the hemidesmosome (3-5). BPA is found within the electron-dense cytoplasmic plaque region of the hemidesmosome. The sequence of cDNA clones encoding the BPA molecule, although not entirely complete, shows no integral membrane segment (J. Stanley, personal communication). Several other monoclonal antibodies specific to hemidesmosomes have been reported, and their antigens await characterization (6, 7). Clearly, other molecules are present in both the cytoplasmic and the extracellular aspect of the hemidesmosome.The molecule(s) that traverses the cell membrane in hemidesmosomes has yet to be identified; candidates include members of the integrin superfamily of extracellular matrix receptors (8-12). The integrins are integral membrane glycoproteins that function as cell-cell and cell-substrate adhesion molecules. As a result of our studies to localize and characterize integrin subunits present in corneal epithelium, we noted that antibodies to both the a6 and (4 integrin subunits bound to the basal cell-basement membrane zone in stationary epithelia. This prompted us to determine whether the heterodimer is associated with hemidesmosomes. The present study reports that a6 and P4 integrins colocalize with BPA and type VII collagen in hemidesmosomes of developing epithelia, that both a6 and (3 antibodies bind to hemidesmosomes as shown by immunoelectron microscopy, and that both a434 and a43l heterodimers can be identified in epithelia by immunoprecipitation. MATERIALS AND METHODSTissue Preparation. For adult corneal epithelium, New Zealand White (NZW) ...

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“…GelB expression in the epithelium spreads progressively distal to the migrating front once wound resurfacing is complete and persists for several weeks thereafter (32,36). The timing correlates with the period during which provisional wound matrix is resorbed and new structures for epithelial/stromal adhesion are assembled in the epithelial basement membrane zone (37). Overexpres-sion of gelB is associated with defective re-epithelialization and a reduction in adhesion complex integrity (23,31).…”

mentioning

confidence: 99%

Matrix Metalloproteinase Gelatinase B (MMP-9) Coordinates and Effects Epithelial Regeneration

Mohan

Chintala

Jung

et al. 2002

Journal of Biological Chemistry

262

205

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We studied the role of the matrix metalloproteinase gelatinase B (gelB; MMP-9) in epithelial regeneration using the gelB-deficient mouse. We report the novel finding that, in contrast to other MMPs expressed at the front of the advancing epithelial sheet in wounds of cornea, skin, or trachea, gelB acts to inhibit the rate of wound closure. We determined this to be due to control of cell replication, a novel capacity for MMPs not previously described. We also found that gelB delays the inflammatory response. Acceleration of these processes in gelB-deficient mice is correlated with a delay in signal transduction through Smad2, a transcription factor that inhibits cell proliferation, and in accumulation of epithelial-associated interleukin-1␣, a cytokine that inhibits Smad2 signaling and promotes the inflammatory response. GelB-deficient mice also reveal defects in remodeling of extracellular matrix at the epithelial basement membrane zone, in particular, failure to effectively remove the fibrin(ogen) provisional matrix. We conclude that gelB coordinates and effects multiple events involved in the process of epithelial regeneration.

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Hemidesmosomes and anchoring fibril collagen appear synchronously during development and wound healing

Cited by 89 publications

References 23 publications

Expression of integrins and basement membrane components by wound keratinocytes.

Expression of integrins and basement membrane components by wound keratinocytes.

Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes.

Matrix Metalloproteinase Gelatinase B (MMP-9) Coordinates and Effects Epithelial Regeneration

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