title: Macrophage PPARγ and impaired wound healing in type 2 diabetes.
abstract: Macrophages undergo a transition from pro-inflammatory to healing-associated phenotypes that is critical for efficient wound healing. However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up-regulation of the peroxisome proliferator-activated receptor (PPAR)γ and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up-regulation of PPARγ activity was impaired by sustained expression of IL-1β in both mouse and human wounds. In addition, experiments with myeloid-specific PPARγ knockout mice indicated that loss of PPARγ in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore, PPARγ agonists promoted a healing-associated macrophage phenotype both in vitro and in vivo, even in the diabetic wound environment. Importantly, topical administration of PPARγ agonists improved healing in diabetic mice, suggesting an appealing strategy for down-regulating inflammation and improving the healing of chronic wounds.
authors: Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, USA.
authors: Rita E
authors: RE
authors: Mirza
authors: Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, USA.
authors: Milie M
authors: MM
authors: Fang
authors: Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, USA.
authors: Margaret L
authors: ML
authors: Novak
authors: Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, USA.|Center for Tissue Repair and Regeneration, University of Illinois, Chicago, IL, USA.
authors: Norifumi
authors: N
authors: Urao
authors: Department of Surgery, University of Illinois, Chicago, IL, USA.
authors: Audrey
authors: A
authors: Sui
authors: Department of Surgery, University of Illinois, Chicago, IL, USA.|Center for Tissue Repair and Regeneration, University of Illinois, Chicago, IL, USA.
authors: William J
authors: WJ
authors: Ennis
authors: Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, USA.|Center for Tissue Repair and Regeneration, University of Illinois, Chicago, IL, USA.
authors: Timothy J
authors: TJ
authors: Koh
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007871:Leg Ulcer / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000235:genetics; D000077154:Rosiglitazone; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D045162:Thiazolidinediones / Q000008:administration & dosage; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
chemical_list: C477819:15-deoxyprostaglandin J2; C508585:IL1B protein, human; C587672:IL1B protein, mouse; C583355:IL1R1 protein, mouse; D053583:Interleukin-1beta; D047495:PPAR gamma; D053573:Receptors, Interleukin-1 Type I; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015230:Prostaglandin D2
keywords: diabetes; inflammation; macrophage; resolution of inflammation; wound healing