Impaired skin wound healing in lumican-null mice.
BACKGROUND
Previous studies have demonstrated that the lack of lumican delayed corneal wound healing in lumican-null (Lum(-/-) ) mice. This defect is rescued by the addition of glycosylated lumican core protein to the injured corneas.


OBJECTIVE
We examined the hypothesis that lumican is also required for the healing of cutaneous wounds using Lum(-/-) mice.


METHODS
We demonstrated the basic thinner skin phenotypes in Lum(-/-) mice at different time points and the changes in arrangement of collagen fibres by transmission electron microscopy (TEM). A full skin thickness wound was generated by punch biopsy (6 mm diameter) in experimental Lum(-/-) and wild-type mice. The closure of injured skin was measured after various periods of time (3, 6, 12, 18 days). Specimens of injured and uninjured skin (serving as control) were then subjected to morphological examination with haematoxylin and eosin and Masson trichrome stains, and by TEM. Immunohistochemical staining with anti-CD68 antibody was used to assess the presence of macrophages in injured skin healing for various periods of time. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to elucidate the transforming growth factor (TGF)-β1-induced myofibroblast phenotypic genes.


RESULTS
Skin of adult Lum(-/-) mice (3 months and older) was much thinner (40% less) than that of age-matched wild-type mice. This phenomenon was aggravated in older mice. TEM revealed disoriented and irregular collagen fibrils in the dermis of Lum(-/-) mice. Delayed wound healing with an increase in inflammatory macrophages was compatible with the delayed response of the expression of TGF-β1, type I collagen α1 and fibronectin at the mRNA level by semiquantitative RT-PCR in the Lum(-/-) mice.


CONCLUSIONS
Our data demonstrate that lumican plays pivotal roles in skin collagen fibrillogenesis and wound healing.
Yeh
J-T
JT
Division of Trauma, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 105, Taiwan.
Yeh
L-K
LK
Jung
S-M
SM
Chang
T-J
TJ
Wu
H-H
HH
Shiu
T-F
TF
Liu
C-Y
CY
Kao
W W-Y
WW
Chu
P-H
PH
D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D007150:Immunohistochemistry; D007632:Keratan Sulfate / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071234:Lumican; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D011508:Chondroitin Sulfate Proteoglycans; D005353:Fibronectins; C000604307:Lum protein, mouse; D000071234:Lumican; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D003094:Collagen; D007632:Keratan Sulfate