Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing.
Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.
Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, China.
Huichen
H
Zhao
Department of Cell Biology, Shandong University School of Medicine, Jinan, China.|Department of Blood Transfusion of Qilu Hospital, Shandong University, Jinan, China.
Jicui
J
Chen
Department of General Surgery, Qingdao Women and Children`s Hospital, Qingdao, China.
Jiachao
J
Chai
Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, China.
Yuchao
Y
Zhang
Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
Cong
C
Yu
Department of Endocrinology, The Second Hospital of Shandong University, Jinan, China.
Zhe
Z
Pan
Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
Peng
P
Gao
Department of Cell Biology, Shandong University School of Medicine, Jinan, China.
Chen
C
Zong
Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
Qingbo
Q
Guan
Department of Nephrology, The Second Hospital of Shandong University, Jinan, China.
Yuqin
Y
Fu
Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, China.
Yuantao
Y
Liu
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012883:Skin Ulcer / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
C494022:14,15-eicosa-5-enoic acid; C000717353:Cyp2j6 protein, mouse; D016207:Cytokines; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid