Lack of collagen XVIII accelerates cutaneous wound healing, while overexpression of its endostatin domain leads to delayed healing.
Endostatin, the C-terminal fragment of collagen XVIII, is known to suppress tumour growth and angiogenesis by inhibiting endothelial cell proliferation and migration. We have previously shown that endostatin and its precursor are important for the structural organization of basement membranes (BM). The aim of this study was to investigate cutaneous wound healing in mice overexpressing endostatin in keratinocytes (ES-tg) and in mice lacking collagen XVIII (Col18a1(-/-)). Excisional wounds were made on the dorsal skin of mice, the wound areas were measured and the wounds were collected for further analyses after 3, 6 or 14 days. The healing of the wounds was delayed in the ES-tg mice and accelerated in the Col18a1(-/-) mice, and the vascularisation rate was accelerated in the Col18a1(-/-) mice, but not affected in the ES-tg mice. Abnormal capillaries with swollen endothelial cells and narrowed lumens were observed in the wounds of the ES-tg mice. In these mice also the formation of the epidermal BM was delayed, and the structure of the epidermal and capillary BMs was more disorganised. Moreover, detachment of the epidermis from the granulation tissue was observed in half (n=10) of the 6-day-old ES-tg wounds, but in none of the controls, suggesting an increased fragility of the epidermal-dermal junction in the presence of an excess of endostatin.
Seppinen
Lotta
L
Biocenter Oulu, Collagen Research Unit, University of Oulu, Oulu, Finland.
Sormunen
Raija
R
Soini
Ylermi
Y
Elamaa
Harri
H
Heljasvaara
Ritva
R
Pihlajaniemi
Taina
T
D000818:Animals; D017209:Apoptosis; D001485:Basement Membrane / Q000502:physiology; D002196:Capillaries / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D043170:Collagen Type XVIII / Q000235:genetics / Q000378:metabolism*; D043169:Endostatins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*
D043170:Collagen Type XVIII; D043169:Endostatins