Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

Chen, Qing-Ying; Wang, Guo Guang; Li, Wei; Jiang, Yuxin; Lü, Xiaohua; Zhou, Pingping

doi:10.1155/2016/9726503

Cited by 39 publications

(40 citation statements)

References 58 publications

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“…HO catalyzes the degradation of heme to carbon monoxide, a vasoactive gas; biliverdin, an antioxidant; and free iron 40 . The HO system possesses antioxidative and anti-apoptotic properties, and may influence cell proliferation, differentiation, and migration 41 . Therefore, we postulated that the Nrf2-HO system may be involved in mild PAM-induced preconditioning effects.…”

Section: Discussionmentioning

confidence: 99%

“…A relatively low dose of plasma has been reported to induce the proliferation of cells 7 8 , and has potential for clinical applications, for example, wound healing 2 47 48 . On the other hand, the induction of HO-1 has also been reported to play a crucial role in wound healing 41 49 50 . Our results clearly demonstrate that the pretreatment with mild PAM protected fibroblasts from oxidative stress by up-regulating HO-1; tens of μM of H 2 O 2 in mild PAM contribute to preconditioning effects; the H 2 O 2 -induced activation of the Nrf2-ARE signaling pathway needs to be involved in the up-regulation of HO-1 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts

Horiba

Kamiya

Hara

et al. 2017

Sci Rep

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Non-thermal atmospheric pressure plasma (NTAPP) has recently been applied to living cells and tissues and has emerged as a novel technology for medical applications. NTAPP affects cells not only directly, but also indirectly with previously prepared plasma-activated medium (PAM). The objective of this study was to demonstrate the preconditioning effects of "mild PAM" which was prepared under relatively mild conditions, on fibroblasts against cellular injury generated by a high dose of hydrogen peroxide (H 2 O 2 ). We observed the preconditioning effects of mild PAM containing approximately 50 μM H 2 O 2 . Hydrogen peroxide needs to be the main active species in mild PAM for it to exert preconditioning effects because the addition of catalase to mild PAM eliminated these effects. The nuclear translocation and recruitment of nuclear factor erythroid 2-related factor 2 (Nrf2) to antioxidant response elements (ARE) in heme oxygenase 1 (HO-1) promoters and the up-regulation of HO-1 were detected in fibroblasts treated with mild PAM. The addition of ZnPP, a HO-1-specific inhibitor, or the knockdown of Nrf2 completely abrogated the preconditioning effects. Our results demonstrate that mild PAM protects fibroblasts from oxidative stress by up-regulating HO-1, and the H 2 O 2 -induced activation of the Nrf2-ARE pathway needs to be involved in this reaction.Plasma is the fourth state of matter and is defined as an ionized gas. According to its gas temperature, plasma has been divided into thermal and non-thermal plasma. Non-thermal atmospheric pressure plasma (NTAPP) has recently been applied to living cells and tissues 1 and has emerged as a novel technology for clinical medicine, for example, wound healing 2 , blood coagulation 3 , sterilization 4 , and cancer treatments 1,5,6 . In these studies on its clinical application, a low dose of NTAPP was reported to induce the proliferation of cells, whereas a high dose induced apoptosis 7 . NTAPP contains variable compositions of ultraviolet light, free electrons, and charged particles as well as reactive oxygen species (ROS) such as the hydroxyl radical (• OH), superoxide (O 2 − ), ozone (O 3 ), and hydrogen peroxide (H 2 O 2 ), and reactive nitrogen species (RNS) including nitric oxide (NO• ) and peroxynitrite (ONOO − ) 8,9 . Most of the functions of NTAPP are involved in the activities of ROS and/or RNS [10][11][12] . ROS affect several signaling pathways in cells such as protein kinases, transcription factors, and cellular signaling proteins 13 . High levels of intracellular ROS are known to be harmful because they trigger significant oxidative damage in cellular macromolecules, such as nucleotides, lipid, and proteins, whereas low levels of intracellular ROS are necessary for a number of important physiological functions including intracellular signal transduction and host defenses against microorganisms 14 . "Preconditioning" is a phenomenon in which brief oxidative stress induced by low levels of ROS may result in protection against a subsequent stronger stress. The Ke...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts

Horiba

Kamiya

Hara

et al. 2017

Sci Rep

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“…HO-1, an inducible rate-limiting enzyme, catalyzes heme into equimolar amounts of carbon monoxide (CO), biliverdin and free iron. Induction of HO-1 may protect against oxidative stress-related cell and tissue injury ( 40 , 43 ). Biliverdin has been confirmed to be a potent antioxidant ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Taurine alleviates lipopolysaccharide-induced liver injury by anti-inflammation and antioxidants in rats

Liu

Zhang

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to investigate the protective effect of taurine on lipopolysaccharide (LPS)-induced liver injury and its mechanisms. Male rats were randomly divided into three groups: Normal saline, LPS model and taurine treatment. Experimental animals were treated with saline or taurine (dissolved in saline, 200 mg/kg/day) via intravenous injection. After 2 h, saline or LPS (0.5 mg/kg) was administrated via intraperitoneal injection. Markers of liver injury, pro-inflammatory cytokines and superoxide dismutase (SOD) activity were determined in plasma. Liver tissues were removed for morphological analysis and determination by western blot analysis. Taurine significantly reduced the elevation in the levels of LPS-induced aspartate transaminase and alanine transaminase and decreased the concentrations of LPS-induced inflammatory factors including tumor necrosis factor-α and interleukin-6. Taurine also increased the activity of SOD in serum and the expression of heme oxygenase-1 protein in liver tissue. Taurine pretreatment also reduced the elevated expression levels of LPS-induced cyclooxygenase-2, nuclear factor κB and extracellular regulated protein kinase. The results from the present study demonstrated that taurine alleviates LPS-induced liver injury. The beneficial role of taurine may be associated with its reduction of pro-inflammatory response and oxidative stress.

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“…The process of skin healing in diabetes often results in elevated levels of inflammatory mediators and oxygen radicals, with sustained levels of hyperglycemia associated with endothelial cell damage and vascular wound dysfunction. Impaired wound healing may be characterized by ischemia arising from severe infection and damage to the granulation tissue formation of the wound . There are numerous defects involved in the process of wound healing in diabetic individuals, including abnormal cell migration, proliferation, and insufficient extracellular matrix depositions …”

Section: Introductionmentioning

confidence: 99%

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF‐1α pathway by improving the blood preservation solution

Zhu

Yongquan

et al. 2020

FASEB j.

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Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF‐1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF‐1α pathway were determined by measuring expression of VEGF, EGF, HIF‐1α, and HSP‐90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF‐1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α‐SMA in skin tissues, and reduced TNF‐α, IL‐1β, and IL‐6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF‐1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF‐1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF‐1α pathway.

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Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

Cited by 39 publications

References 58 publications

Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts

Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts

Taurine alleviates lipopolysaccharide-induced liver injury by anti-inflammation and antioxidants in rats

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF‐1α pathway by improving the blood preservation solution

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