TY - JOUR
T1 - Limitations of Knockout Mice and Other Tools in Assessment of the Involvement of Matrix Metalloproteinases in Wound Healing and the Means to Overcome Them
AU - Nguyen, Trung T.
AU - Wolter, William R.
AU - Anderson, Bowen
AU - Schroeder, Valerie A.
AU - Gao, Ming
AU - Gooyit, Major
AU - Suckow, Mark A.
AU - Chang, Mayland
N1 - Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/6/12
Y1 - 2020/6/12
N2 - Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation. Furthermore, by spatiotemporal control in the use of a selective MMP-2 inhibitor, along with immunoprecipitation and Western blotting, we provide definitive demonstration that MMP-2 does not affect wound healing, contrary to reports. MMP-2 is found in wounds complexed with TIMPs, which is catalytically incompetent.
AB - Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation. Furthermore, by spatiotemporal control in the use of a selective MMP-2 inhibitor, along with immunoprecipitation and Western blotting, we provide definitive demonstration that MMP-2 does not affect wound healing, contrary to reports. MMP-2 is found in wounds complexed with TIMPs, which is catalytically incompetent.
KW - MMP-13
KW - MMP-2
KW - MMP-8
KW - MMP-knockout
KW - diabetic mice
KW - wound healing
UR - https://www.scopus.com/pages/publications/85088848241
UR - https://www.scopus.com/inward/citedby.url?scp=85088848241&partnerID=8YFLogxK
U2 - 10.1021/acsptsci.9b00109
DO - 10.1021/acsptsci.9b00109
M3 - Article
AN - SCOPUS:85088848241
VL - 3
SP - 489
EP - 495
JO - ACS Pharmacology and Translational Science
JF - ACS Pharmacology and Translational Science
IS - 3
ER -
