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Loss of the desmosomal component perp impairs wound healing in vivo.

Beaudry VG, Ihrie RA, Jacobs SB, Nguyen B, Pathak N, Park E, Attardi LD - Dermatol Res Pract (2010)

Bottom Line: Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound.Furthermore, we determine that while loss of Perp compromises cell-cell adhesion, it does not impair keratinocyte proliferation and actually enhances keratinocyte migration in in vitro assays.Thus, Perp's role in promoting cell adhesion is essential for wound closure.

View Article: PubMed Central - PubMed

Affiliation: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound. Modulation of cell-cell adhesion junctions is thought to facilitate cellular proliferation and migration of keratinocytes across the wound. In particular, desmosomes, adhesion complexes critical for maintaining epithelial integrity, are downregulated at the wound edge. It is unclear, however, how compromised desmosomal adhesion would affect wound reepithelialization, given the need for a delicate balance between downmodulating adhesive strength to permit changes in cellular morphology and maintaining adhesion to allow coordinated migration of keratinocyte sheets. Here, we explore the contribution of desmosomal adhesion to wound healing using mice deficient for the desmosomal component Perp. We find that Perp conditional knockout mice display delayed wound healing relative to controls. Furthermore, we determine that while loss of Perp compromises cell-cell adhesion, it does not impair keratinocyte proliferation and actually enhances keratinocyte migration in in vitro assays. Thus, Perp's role in promoting cell adhesion is essential for wound closure. Together, these studies suggest a role for desmosomal adhesion in efficient wound healing.

No MeSH data available.


Related in: MedlinePlus

Migrating keratinocytes lacking Perp do not exhibit altered proliferation in vivo. (a)–(d) Representative images of Ki67 staining on sections of wounds at various timepoints post injury in control (Perpfl/fl) mice. (e)–(h) Representative images of Ki67 staining of wounds from K14CreER; Perpfl/fl mice. Dashed yellow line surrounds epithelium. DAPI is used to stain nuclei. Arrows indicate Ki67 positive cells. Scale bar equals 50 μm.
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fig5: Migrating keratinocytes lacking Perp do not exhibit altered proliferation in vivo. (a)–(d) Representative images of Ki67 staining on sections of wounds at various timepoints post injury in control (Perpfl/fl) mice. (e)–(h) Representative images of Ki67 staining of wounds from K14CreER; Perpfl/fl mice. Dashed yellow line surrounds epithelium. DAPI is used to stain nuclei. Arrows indicate Ki67 positive cells. Scale bar equals 50 μm.

Mentions: Defective wound closure could reflect alterations in keratinocyte proliferation. Specifically, enhanced cellular proliferation several cell diameters away from the edge is associated with wound reepithelialization [3]. We therefore examined whether the delayed wound healing observed in the absence of Perp was attributable to decreased cellular proliferation at and near the wound margin by staining for Ki67, a proliferation marker. Uninjured regions of control skin exhibit Ki67-positive cells scattered throughout the actively dividing basal layer (Figure 5(a)). One day post wounding, Ki67-positive cells were found in the area proximal to the wound edge (Figure 5(b)). However, at day 5, the epithelial sheet migrating across the wound expressed few Ki67-positive cells (Figure 5(c)). By day 10, Ki67-positive cells were observed throughout the basal layer of the healed epithelium, as in uninjured epidermis (Figure 5(d)). Upon analysis of Perp-deficient mice, we found no clear decrease in the levels of Ki67-positivity post wounding relative to controls (Figures 5(e)–5(h)). We also performed cleaved caspase 3 staining at days 1, 3, 5, and 10 post wounding to determine if there was any depletion of cells in the absence of Perp that could contribute to delayed wound healing, but we found no significant apoptosis in mice of either genotype (data not shown). Thus, altered levels of proliferation or apoptosis do not appear to account for delayed wound healing in Perp-deficient mice.


Loss of the desmosomal component perp impairs wound healing in vivo.

Beaudry VG, Ihrie RA, Jacobs SB, Nguyen B, Pathak N, Park E, Attardi LD - Dermatol Res Pract (2010)

Migrating keratinocytes lacking Perp do not exhibit altered proliferation in vivo. (a)–(d) Representative images of Ki67 staining on sections of wounds at various timepoints post injury in control (Perpfl/fl) mice. (e)–(h) Representative images of Ki67 staining of wounds from K14CreER; Perpfl/fl mice. Dashed yellow line surrounds epithelium. DAPI is used to stain nuclei. Arrows indicate Ki67 positive cells. Scale bar equals 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Migrating keratinocytes lacking Perp do not exhibit altered proliferation in vivo. (a)–(d) Representative images of Ki67 staining on sections of wounds at various timepoints post injury in control (Perpfl/fl) mice. (e)–(h) Representative images of Ki67 staining of wounds from K14CreER; Perpfl/fl mice. Dashed yellow line surrounds epithelium. DAPI is used to stain nuclei. Arrows indicate Ki67 positive cells. Scale bar equals 50 μm.
Mentions: Defective wound closure could reflect alterations in keratinocyte proliferation. Specifically, enhanced cellular proliferation several cell diameters away from the edge is associated with wound reepithelialization [3]. We therefore examined whether the delayed wound healing observed in the absence of Perp was attributable to decreased cellular proliferation at and near the wound margin by staining for Ki67, a proliferation marker. Uninjured regions of control skin exhibit Ki67-positive cells scattered throughout the actively dividing basal layer (Figure 5(a)). One day post wounding, Ki67-positive cells were found in the area proximal to the wound edge (Figure 5(b)). However, at day 5, the epithelial sheet migrating across the wound expressed few Ki67-positive cells (Figure 5(c)). By day 10, Ki67-positive cells were observed throughout the basal layer of the healed epithelium, as in uninjured epidermis (Figure 5(d)). Upon analysis of Perp-deficient mice, we found no clear decrease in the levels of Ki67-positivity post wounding relative to controls (Figures 5(e)–5(h)). We also performed cleaved caspase 3 staining at days 1, 3, 5, and 10 post wounding to determine if there was any depletion of cells in the absence of Perp that could contribute to delayed wound healing, but we found no significant apoptosis in mice of either genotype (data not shown). Thus, altered levels of proliferation or apoptosis do not appear to account for delayed wound healing in Perp-deficient mice.

Bottom Line: Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound.Furthermore, we determine that while loss of Perp compromises cell-cell adhesion, it does not impair keratinocyte proliferation and actually enhances keratinocyte migration in in vitro assays.Thus, Perp's role in promoting cell adhesion is essential for wound closure.

View Article: PubMed Central - PubMed

Affiliation: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound. Modulation of cell-cell adhesion junctions is thought to facilitate cellular proliferation and migration of keratinocytes across the wound. In particular, desmosomes, adhesion complexes critical for maintaining epithelial integrity, are downregulated at the wound edge. It is unclear, however, how compromised desmosomal adhesion would affect wound reepithelialization, given the need for a delicate balance between downmodulating adhesive strength to permit changes in cellular morphology and maintaining adhesion to allow coordinated migration of keratinocyte sheets. Here, we explore the contribution of desmosomal adhesion to wound healing using mice deficient for the desmosomal component Perp. We find that Perp conditional knockout mice display delayed wound healing relative to controls. Furthermore, we determine that while loss of Perp compromises cell-cell adhesion, it does not impair keratinocyte proliferation and actually enhances keratinocyte migration in in vitro assays. Thus, Perp's role in promoting cell adhesion is essential for wound closure. Together, these studies suggest a role for desmosomal adhesion in efficient wound healing.

No MeSH data available.


Related in: MedlinePlus