Anti-oxidative effects of 17 β-estradiol and genistein in human skin fibroblasts and keratinocytes

Savoia, Paola; Raina, Giulia; Camillo, Lara; Farruggio, Serena; Mary, David A.S.G.; Veronese, Federica; Graziola, Francesca; Zavattaro, Elisa; Tiberio, Rossana; Grossini, Elena

doi:10.1016/j.jdermsci.2018.07.007

Cited by 39 publications

(51 citation statements)

References 64 publications

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“…This effect remains active after the removal of the original driving force by the switch from hyperglycemia to normoglycemia. This partly explains the potential mechanism of the hyperglycemia memory (8, 9), and our findings show that ERβ expression or activation (28) may be able to break this kind of loop, and subsequently diminish the hyperglycemia memory.…”

Section: Discussionsupporting

confidence: 55%

ERβ Accelerates Diabetic Wound Healing by Ameliorating Hyperglycemia-Induced Persistent Oxidative Stress

Zhou

Xiao

et al. 2019

Front. Endocrinol.

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Delayed wound healing in diabetic patients is a serious diabetic complication, resulting in major health problems as well as high mortality and disability. The detailed mechanism still needs to be fully understood. In this study, we aim to investigate potential mechanisms and explore an efficient strategy for clinical treatment of diabetic wound healing. Human umbilical endothelial cells were exposed to hyperglycemia for 4 days, then switched to normoglycemia for an additional 4 days. The cells were harvested for the analysis of reactive oxygen species (ROS) generation, gene expression and VEGF signaling pathway. Furthermore, the diabetic wound model was established in rats for the evaluation of wound healing rates under the treatment of either ERβ agonist/antagonist or SOD mimetic MnTBAP. Our results show that transient hyperglycemia exposure results in persistent ROS overgeneration after the switch to normoglycemia, along with suppressed expression of ERβ, SOD2, and the VEGF signaling pathway. Either ERβ expression or activation diminishes ROS generation. In vivo experiments with diabetic rats show that ERβ activation or SOD mimetic MnTBAP diminishes ROS generation in tissues and accelerates diabetic wound healing. Transient hyperglycemia exposure induces ROS generation and suppresses ERβ expression, subsequently resulting in SOD2 suppression with additional elevated ROS generation. This forms a positive-feed forward loop for ROS generation with persistent oxidative stress. ERβ expression or activation breaks this loop and ameliorates this effect, thereby accelerating diabetic wound healing. We conclude that ERβ accelerates diabetic wound healing by ameliorating hyperglycemia-induced persistent oxidative stress. This provides a new strategy for clinical treatment of diabetic wound healing based on ERβ activation.

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Section: Discussionsupporting

confidence: 55%

ERβ Accelerates Diabetic Wound Healing by Ameliorating Hyperglycemia-Induced Persistent Oxidative Stress

Zhou

Xiao

et al. 2019

Front. Endocrinol.

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“…Fibroblasts are the main sites for collagen and elastic fibres synthesis. Although skin fibroblasts are located in the dermis under the epidermis, they are more subjected to oxidative damage . In our experiment, high‐glucose stimulation attenuated proliferation and migration while enhanced oxidative stress in mice skin fibroblasts, which was most serious in that from SIRT3 knockout mice.…”

Section: Discussionmentioning

confidence: 58%

SIRT3 deficiency delays diabetic skin wound healing via oxidative stress and necroptosis enhancement

Yang

Meng

et al. 2020

J Cellular Molecular Medi

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Sirtuin 3 (SIRT3) plays a vital role in several dermatological diseases. However, the role and detailed mechanism of SIRT3 in diabetic wound healing are unknown well yet. To explore possible involvement of SIRT3 and necroptosis in diabetic skin wound healing, SIRT3 knockout (KO) mice and 129S1/SvImJ wild‐type (WT) mice were injected with streptozotocin (STZ), and mice skin fibroblasts were exposed to high glucose (HG). It was found that SIRT3 expression decreased in the skin of diabetic patients. SIRT3 deficiency delayed healing rate, reduced blood supply and vascular endothelial growth factor expression, promoted superoxide production, increased malondialdehyde (MDA) levels, decreased total antioxidant capacity (T‐AOC), reduced superoxide dismutase (SOD) activity and aggravated ultrastructure disorder in skin wound of diabetic mice. SIRT3 deficiency inhibited mice skin fibroblasts migration with HG stimulation, which was restored by SIRT3 overexpression. SIRT3 deficiency also suppressed α‐smooth muscle actin (α‐SMA) expression, enhanced superoxide production but decreased mitochondrial membrane potential with HG stimulation after scratch. SIRT3 deficiency further elevated receptor‐interacting protein kinase 3 (RIPK3), RIPK1 and caspase 3 expression both in vitro and in vivo. Collectively, SIRT3 deficiency delayed skin wound healing in diabetes, the mechanism might be related to impaired mitochondria function, enhanced oxidative stress and increased necroptosis. This may provide a novel therapeutic target to accelerate diabetic skin wound healing.

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“…Research showed that genistein is a phytoestrogen that can prevent the aging process due to its antioxidant activity. Genistein can decrease the activation/expression of eNOS and iNOS induced by hydrogen peroxide-induced peroxidative stimulation [19]. In addition to its antioxidant properties and estrogenic/antiestrogenic activity, genistein has several molecular roles, including inhibition of protein tyrosine kinase and topoisomerase II and degradation of phosphatidylinositol and proteins involved in multidrug resistance in cancer cells.…”

Section: Genistein As Antioxidantmentioning

confidence: 99%

Antioxidant Activities of Genistein: A Review

Burhan¹,

Oktavia²,

Fauziah³

2020

IJPSM

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Anti-oxidative effects of 17 β-estradiol and genistein in human skin fibroblasts and keratinocytes

Abstract: 17 β-estradiol/genistein protected fibroblasts/keratinocytes against peroxidation by modulating oxidant/antioxidant system and mitochondria membrane potential, through mechanisms related to ERs and GPER30 and kinases activation.

Cited by 39 publications

References 64 publications

ERβ Accelerates Diabetic Wound Healing by Ameliorating Hyperglycemia-Induced Persistent Oxidative Stress

ERβ Accelerates Diabetic Wound Healing by Ameliorating Hyperglycemia-Induced Persistent Oxidative Stress

SIRT3 deficiency delays diabetic skin wound healing via oxidative stress and necroptosis enhancement

Antioxidant Activities of Genistein: A Review

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