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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

Wounded K14CreER;  Perpfl/fl mice exhibit delays in reepithelialization. (a) Cartoon sketch depicting the different stages occurring during the wound healing process. The black dashed line marks the boundary between the epidermis and dermis. Black dashed box demarcates region with migrating keratinocytes, as shown in panel (c). Red dashed box represents region of fully closed wound, as shown in panel (d). EP signifies epidermis and D, dermis. (b) Representative H&E-stained section of open wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER;  Perpfl/fl mice 1 day post wounding. (c) Representative H&E-stained section of wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER;  Perpfl/fl mice 5 days post wounding. The migrating epithelial sheets are outlined by the black dashed line. (d) Representative H&E-stained section of closed wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER;  Perpfl/fl mice 10 days post wounding. Sizes of boxes in (b) and (c) were determined by the edges of the wound, as marked by the panniculus carnosus.
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fig3: Wounded K14CreER; Perpfl/fl mice exhibit delays in reepithelialization. (a) Cartoon sketch depicting the different stages occurring during the wound healing process. The black dashed line marks the boundary between the epidermis and dermis. Black dashed box demarcates region with migrating keratinocytes, as shown in panel (c). Red dashed box represents region of fully closed wound, as shown in panel (d). EP signifies epidermis and D, dermis. (b) Representative H&E-stained section of open wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER; Perpfl/fl mice 1 day post wounding. (c) Representative H&E-stained section of wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER; Perpfl/fl mice 5 days post wounding. The migrating epithelial sheets are outlined by the black dashed line. (d) Representative H&E-stained section of closed wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER; Perpfl/fl mice 10 days post wounding. Sizes of boxes in (b) and (c) were determined by the edges of the wound, as marked by the panniculus carnosus.

Mentions: To further examine the wound healing process in the cohorts, histological analysis of transverse sections of wound sites from both control and K14CreER; Perpfl/fl mice was performed 1, 5, 7, and 10 days post wounding (Figure 3, data not shown). These analyses revealed that while reepithelialization typically neared completion in the control mice by day 5, the epithelial cells had not fully migrated across wounds in the K14CreER; Perpfl/fl mice (Figure 3(c)). In addition, by day 7, many of the wounds in control mice were not only fully reepithelialized but had reestablished normal epidermal architecture (data not shown). In contrast, in the K14CreER; Perpfl/fl mice, keratinocytes had migrated across the wound but had not yet formed a full thickness skin layer by day 7 (data not shown). By day 10, both cohorts of mice exhibited fully reepithelialized wounds (Figure 3(d)). These data reinforce our observations at the macroscopic level that Perp loss delays wound healing after cutaneous injury.


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)

Wounded K14CreER;  Perpfl/fl mice exhibit delays in reepithelialization. (a) Cartoon sketch depicting the different stages occurring during the wound healing process. The black dashed line marks the boundary between the epidermis and dermis. Black dashed box demarcates region with migrating keratinocytes, as shown in panel (c). Red dashed box represents region of fully closed wound, as shown in panel (d). EP signifies epidermis and D, dermis. (b) Representative H&E-stained section of open wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER;  Perpfl/fl mice 1 day post wounding. (c) Representative H&E-stained section of wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER;  Perpfl/fl mice 5 days post wounding. The migrating epithelial sheets are outlined by the black dashed line. (d) Representative H&E-stained section of closed wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER;  Perpfl/fl mice 10 days post wounding. Sizes of boxes in (b) and (c) were determined by the edges of the wound, as marked by the panniculus carnosus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Wounded K14CreER; Perpfl/fl mice exhibit delays in reepithelialization. (a) Cartoon sketch depicting the different stages occurring during the wound healing process. The black dashed line marks the boundary between the epidermis and dermis. Black dashed box demarcates region with migrating keratinocytes, as shown in panel (c). Red dashed box represents region of fully closed wound, as shown in panel (d). EP signifies epidermis and D, dermis. (b) Representative H&E-stained section of open wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER; Perpfl/fl mice 1 day post wounding. (c) Representative H&E-stained section of wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER; Perpfl/fl mice 5 days post wounding. The migrating epithelial sheets are outlined by the black dashed line. (d) Representative H&E-stained section of closed wounds from tamoxifen-injected control (Perpfl/fl) and K14CreER; Perpfl/fl mice 10 days post wounding. Sizes of boxes in (b) and (c) were determined by the edges of the wound, as marked by the panniculus carnosus.
Mentions: To further examine the wound healing process in the cohorts, histological analysis of transverse sections of wound sites from both control and K14CreER; Perpfl/fl mice was performed 1, 5, 7, and 10 days post wounding (Figure 3, data not shown). These analyses revealed that while reepithelialization typically neared completion in the control mice by day 5, the epithelial cells had not fully migrated across wounds in the K14CreER; Perpfl/fl mice (Figure 3(c)). In addition, by day 7, many of the wounds in control mice were not only fully reepithelialized but had reestablished normal epidermal architecture (data not shown). In contrast, in the K14CreER; Perpfl/fl mice, keratinocytes had migrated across the wound but had not yet formed a full thickness skin layer by day 7 (data not shown). By day 10, both cohorts of mice exhibited fully reepithelialized wounds (Figure 3(d)). These data reinforce our observations at the macroscopic level that Perp loss delays wound healing after cutaneous injury.

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