Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 135, Issue 10, Pages 2377-2384Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2015.167
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Funding
- NCI NIH HHS [R01 CA177272] Funding Source: Medline
- NHLBI NIH HHS [HL089455, R01 HL089455, HL098067, P01 HL098067, R21 HL093385] Funding Source: Medline
- NIAMS NIH HHS [F32 AR060157, AR060157] Funding Source: Medline
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Matrix metalloproteinase-10 (MMP-10) is expressed by macrophages and epithelium in response to injury, but its functions in wound repair are unknown. We observed increased collagen deposition and skin stiffness in Mmp10(-/-) wounds, with no difference in collagen expression or reepithelialization. Increased collagen deposition in Mmp10(-/-) wounds was accompanied by less collagenolytic activity and reduced expression of specific metallocollagenases, particularly MMP-8 and MMP-13, where MMP-13 was the key collagenase. Ablation and adoptive transfer approaches and cell-based models demonstrated that the MMP-10-dependent collagenolytic activity was a product of alternatively activated (M2) resident macrophages. These data demonstrate a critical role for macrophage MMP-10 in controlling the tissue remodeling activity of macrophages and moderating scar formation during wound repair.
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