Adiponectin Regulates Cutaneous Wound Healing by Promoting Keratinocyte Proliferation and Migration via the ERK Signaling Pathway

Abstract

Diabetic patients are at high risk of developing delayed cutaneous wound healing. Adiponectin plays a pivotal role in the pathogenesis of diabetes and is considered to be involved in various pathological conditions associated with diabetes; however, its role in wound repair is unknown. In this study, we elucidated the involvement of adiponectin in cutaneous wound healing in vitro and in vivo. Normal human keratinocytes expressed adiponectin receptors, and adiponectin enhanced proliferation and migration of keratinocytes in vitro. This proliferative and migratory effect of adiponectin was mediated via AdipoR1/AdipoR2 and the ERK signaling pathway. Consistent with in vitro results, wound closure was significantly delayed in adiponectin-deficient mice compared with wild-type mice, and more importantly, keratinocyte proliferation and migration during wound repair were also impaired in adiponectin-deficient mice. Furthermore, both systemic and topical administration of adiponectin ameliorated impaired wound healing in adiponectin-deficient and diabetic db/db mice, respectively. Collectively, these results indicate that adiponectin is a potent mediator in the regulation of cutaneous wound healing. We propose that upregulation of systemic and/or local adiponectin levels is a potential and very promising therapeutic approach for dealing with diabetic wounds.

Adiponectin: Serum-saliva associations and relations with oral and systemic markers of inflammation

“…For example, a positive effect of total adiponectin on skin keratinocyte proliferation has been reported in mice where adiponectin was directly associated with cutaneous wound healing (Shibata et al, 2012), and this effect was confirmed in human periodontal ligament (PDL) cells (Nokhbehsaim et al, 2014). However, a study in human gingival keratinocytes (GK) found no effect of total adiponectin alone on cell proliferation and an inhibitive effect in combination with P. gingivalis LPS (Kraus et al, 2012).…”

Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

“…In the gene networks in T-lep lesions, MMP9 and MMP12 were connected by the common gene ontology terms: "chemotaxis" and "tissue remodeling". As part of this network, other genes involved in "chemotaxis" and "tissue remodeling" included IRF6, ADIPOQ, OVOL1, and FOXQ1 (43)(44)(45)(46)(47)(48). Another prominent gene, CYP27B1, a member of the cytochrome p450 family, is a critical part of the vitamin D antimicrobial pathway to kill mycobacteria (16,25,49,50).…”

Adiponectin as a tissue regenerating hormone: more than a metabolic function

“…In particular, mice lacking adiponectin develop irreversible albuminuria and renal failure, while those overexpressing fAd show a more rapid recovery and a decreased formation of fibrosis compared to control mice [79]. Furthermore, adiponectin KO mice show a significantly delayed wound closure compared with wild-type mice [80]. In particular, fAd promotes the proliferation and the migration of healthy human keratinocytes through AdipoR1/AdipoR2 and the MAPK signaling pathway.…”

“…In particular, fAd promotes the proliferation and the migration of healthy human keratinocytes through AdipoR1/AdipoR2 and the MAPK signaling pathway. Systemic and topical administration of the hormone in adiponectin-deficient and diabetic db/db mice ameliorates wound repair, thus indicating fAd as a potent mediator of cutaneous wound healing [80].…”