期刊
BRITISH JOURNAL OF DERMATOLOGY
卷 163, 期 6, 页码 1174-1180出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2133.2010.10008.x
关键词
lumican; macrophage; skin injury; wound healing
类别
资金
- National Sciences Council, Taiwan [NSC 972314B182A059, 982314B182A029MY3, NSC 94-2314-B-182-071, 95-2314-B-182-021]
- NIH [EY011845]
- Research to Prevent Blindness
- Ohio Lion's Eye Research Foundation
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. Objectives 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)-beta 1-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-beta 1, type I collagen alpha 1 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.
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