R‐Ras regulates vascular permeability, but not overall healing in skin wounds

Wounds close by keratinocytes migrating from the edge of the wound and re‐epithelializing the epidermis. It has been proposed that the major stimuli for wound closure are blood‐derived growth factors, chemokines and cytokines. The small GTPase R‐Ras, a known integrin activator, also regulates vascul...

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Bibliographic Details
Published in:Experimental dermatology 2019-02, Vol.28 (2), p.202-206
Main Authors: Ketomäki, Tuomo, Vähätupa, Maria, May, Ulrike, Pemmari, Toini, Ruikka, Ella, Hietamo, Jussi, Kaipiainen, Pirkka, Barker, Harlan, Parkkila, Seppo, Uusitalo‐Järvinen, Hannele, Järvinen, Tero A. H.
Format: Article
Language:English
Subjects:
Angiogenesis
Blood vessels
Chemokines
Cytokines
Epidermis
Growth factors
Guanosine triphosphatases
integrin
Keratinocytes
Muscles
Permeability
Plasma proteins
Proteins
R‐Ras
Skin
vascular permeability
wound
Wound healing
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Summary:Wounds close by keratinocytes migrating from the edge of the wound and re‐epithelializing the epidermis. It has been proposed that the major stimuli for wound closure are blood‐derived growth factors, chemokines and cytokines. The small GTPase R‐Ras, a known integrin activator, also regulates vascular permeability during angiogenesis, and blood vessels lacking R‐Ras leak plasma proteins constantly. We explored whether the access to blood‐derived proteins influences skin wound healing in R‐Ras knockout (KO) mice. In skin wounds, R‐Ras expression was mostly restricted to the vasculature in the granulation tissue. Angiogenic blood vessels in the R‐Ras KO mice were significantly more permeable than in wild‐type (WT) controls. Although the distances between epidermal tongues, and the panniculus carnosus muscles, were significantly longer in R‐Ras KO than WT controls before the granulation tissue formation took place, there were no differences in the wound closure or re‐epithelialization rates or granulation tissue formation. These findings were also corroborated in a special splint excision wound model. Our study shows that although R‐Ras does not influence the skin wound healing itself, the blood vessels lacking R‐Ras are leaky and thus could facilitate the access of blood‐derived proteins to the wound.
ISSN:0906-6705
1600-0625
DOI:10.1111/exd.13851