期刊
MATRIX BIOLOGY
卷 21, 期 2, 页码 149-161出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0945-053X(01)00192-5
关键词
MMP-13 promoter; cutaneous wound healing; transgenic mice; collagenase
资金
- NIA NIH HHS [AG 06528, R01 AG006528] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [R01AG006528] Funding Source: NIH RePORTER
Cutaneous wound repair involves extracellular matrix degradation. cell migration. matrix resynthesis and tissue remodeling. In the rodent. transcriptional regulation of collagenase-3 (MMP-13) most likely plays a role in these processes. Therefore, we isolated and characterized a 1.76-kb 5'-flanking region of the mouse MMP-13 gene. Assay of promoter activity by transient transfection of HT1080 cells and primary mouse skin fibroblasts allowed identification of several functional regions of the 5'-flanking DNA. Expression of luciferase reporter constructs in these cells was induced by phorbol myristate acetate (PMA), but not by transforming growth factor-beta(2) (TGF-beta(2)). To study the regulation of MMP-13 in cutaneous wound beating, we generated transgenic mouse lines harboring the firefly luciferase reporter gene under control of a 660-bp mouse MMP-13 promoter which showed maximal response. MMP-13 mRNA levels in transgenic lung fibroblasts increased 1.5-2.6-fold after PMA challenge. MMP-13 promoter activity in wounds was visualized and quantified in vivo as luciferase bioluminescence. MMP-13 expression was present at day 1 and maximal at day 18 post-wounding. Luciferase activity progressed from the wound margin towards the center of the wound. In situ hybridization showed the same spatial and temporal patterns for the luciferase and endogenous MMP-13 mRNA. Both signals localized predominantly to dermal fibroblasts at the wound periphery but not to granulation tissue or to keratinocytes. These results suggested that MMP-13 participated in the wound healing of acute wounds. and it was a significant factor in long-term remodeling of wound connective tissue in rodent skin. (C) 2002 Elsevier Science B.V. and International Society of Matrix Biology. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据