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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

Loss of Perp delays wound healing in vivo. (a) Representative photos of dorsal skin bearing open wounds at the beginning of the study and fully closed wounds at the end of the study. (b) Graph displays the average area of all wounds as a function of time post-biopsy. Combined controls: n = 64 wounds amongst 16 mice. K14CreER;  Perpfl/fl mice: n = 32 wounds amongst 8 mice. Error bars represent the SEM. Statistical significance was determined using ANOVA * = P < .03.
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fig2: Loss of Perp delays wound healing in vivo. (a) Representative photos of dorsal skin bearing open wounds at the beginning of the study and fully closed wounds at the end of the study. (b) Graph displays the average area of all wounds as a function of time post-biopsy. Combined controls: n = 64 wounds amongst 16 mice. K14CreER; Perpfl/fl mice: n = 32 wounds amongst 8 mice. Error bars represent the SEM. Statistical significance was determined using ANOVA * = P < .03.

Mentions: To assay wound reepithelialization, we subjected mice in the Perp-deficient and control cohorts to full skin thickness punch biopsies. The experimental cohort consisted of tamoxifen-treated K14CreER; Perpfl/fl mice, while the control cohorts comprised tamoxifen-treated K14CreER; Perp+/+, Perpfl/+, and Perpfl/fl mice as well as untreated Perpfl/fl, Perpfl/+, K14CreER; Perpfl/fl, and K14CreER; Perpfl/+ mice. Four 6 mm punches were performed on each mouse, and the sizes of the wounds were measured daily for approximately 10 days to determine the rate of wound closure. We found that mice lacking Perp in the epithelial compartment exhibited a delay in wound healing relative to controls, underscoring the importance of Perp in the wound healing process (Figures 2(a), and 2(b)).


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)

Loss of Perp delays wound healing in vivo. (a) Representative photos of dorsal skin bearing open wounds at the beginning of the study and fully closed wounds at the end of the study. (b) Graph displays the average area of all wounds as a function of time post-biopsy. Combined controls: n = 64 wounds amongst 16 mice. K14CreER;  Perpfl/fl mice: n = 32 wounds amongst 8 mice. Error bars represent the SEM. Statistical significance was determined using ANOVA * = P < .03.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902749&req=5

fig2: Loss of Perp delays wound healing in vivo. (a) Representative photos of dorsal skin bearing open wounds at the beginning of the study and fully closed wounds at the end of the study. (b) Graph displays the average area of all wounds as a function of time post-biopsy. Combined controls: n = 64 wounds amongst 16 mice. K14CreER; Perpfl/fl mice: n = 32 wounds amongst 8 mice. Error bars represent the SEM. Statistical significance was determined using ANOVA * = P < .03.
Mentions: To assay wound reepithelialization, we subjected mice in the Perp-deficient and control cohorts to full skin thickness punch biopsies. The experimental cohort consisted of tamoxifen-treated K14CreER; Perpfl/fl mice, while the control cohorts comprised tamoxifen-treated K14CreER; Perp+/+, Perpfl/+, and Perpfl/fl mice as well as untreated Perpfl/fl, Perpfl/+, K14CreER; Perpfl/fl, and K14CreER; Perpfl/+ mice. Four 6 mm punches were performed on each mouse, and the sizes of the wounds were measured daily for approximately 10 days to determine the rate of wound closure. We found that mice lacking Perp in the epithelial compartment exhibited a delay in wound healing relative to controls, underscoring the importance of Perp in the wound healing process (Figures 2(a), and 2(b)).

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