MMP-10 Regulates Collagenolytic Activity of Alternatively Activated Resident Macrophages.
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.
Center for Lung Biology, University of Washington, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA. Electronic address: maryam.rohani@cshs.org.
Maryam G
MG
Rohani
Center for Lung Biology, University of Washington, Seattle, Washington, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA.
Ryan S
RS
McMahan
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Maria V
MV
Razumova
Center for Lung Biology, University of Washington, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA.
Angie L
AL
Hertz
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Maryelise
M
Cieslewicz
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Suzie H
SH
Pun
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Michael
M
Regnier
Center for Lung Biology, University of Washington, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Ying
Y
Wang
Center for Lung Biology, University of Washington, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA.
Timothy P
TP
Birkland
Center for Lung Biology, University of Washington, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
William C
WC
Parks
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002478:Cells, Cultured; D002921:Cicatrix / Q000517:prevention & control; D017364:Collagenases / Q000378:metabolism*; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012038:Regeneration / Q000502:physiology; D012680:Sensitivity and Specificity; D012867:Skin / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology; D014947:Wounds and Injuries / Q000201:enzymology* / Q000473:pathology
D017364:Collagenases; D053506:Matrix Metalloproteinase 10; D020784:Matrix Metalloproteinase 8