Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound

2021 ◽  
Author(s):  
Shuangwen Li ◽  
Yuan Li ◽  
Ziyu Wu ◽  
Zhongming Wu ◽  
Hongjuan Fang
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Major Complication ◽  
Lipid Peroxides ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Wound Site

Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides, in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins, and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.

scholarly journals Shedding Light on a New Treatment for Diabetic Wound Healing: A Review on Phototherapy

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Nicolette N. Houreld
Keyword(s):  
Wound Healing ◽  
Laser Irradiation ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
Intensity Laser

Impaired wound healing is a common complication associated with diabetes with complex pathophysiological underlying mechanisms and often necessitates amputation. With the advancement in laser technology, irradiation of these wounds with low-intensity laser irradiation (LILI) or phototherapy, has shown a vast improvement in wound healing. At the correct laser parameters, LILI has shown to increase migration, viability, and proliferation of diabetic cellsin vitro; there is a stimulatory effect on the mitochondria with a resulting increase in adenosine triphosphate (ATP). In addition, LILI also has an anti-inflammatory and protective effect on these cells. In light of the ever present threat of diabetic foot ulcers, infection, and amputation, new improved therapies and the fortification of wound healing research deserves better prioritization. In this review we look at the complications associated with diabetic wound healing and the effect of laser irradiation bothin vitroandin vivoin diabetic wound healing.

scholarly journals Increasing Angiogenesis Factors in Hypoxic Diabetic Wound Conditions by siRNA Delivery: Additive Effect of LbL-Gold Nanocarriers and Desloratadine-Induced Lysosomal Escape

2021 ◽  
Vol 22 (17) ◽  
pp. 9216
Author(s):  
Elnaz Shaabani ◽  
Maryam Sharifiaghdam ◽  
Joris Lammens ◽  
Herlinde De Keersmaecker ◽  
Chris Vervaet ◽  
...  
Keyword(s):  
Wound Healing ◽  
Transfection Efficiency ◽  
Endosomal Escape ◽  
Regulatory Control ◽  
Induced Response ◽  
Layer By Layer ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Angiogenesis Factors

Impaired wound healing in people with diabetes has multifactorial causes, with insufficient neovascularization being one of the most important. Hypoxia-inducible factor-1 (HIF-1) plays a central role in the hypoxia-induced response by activating angiogenesis factors. As its activity is under precise regulatory control of prolyl-hydroxylase domain 2 (PHD-2), downregulation of PHD-2 by small interfering RNA (siRNA) could stabilize HIF-1α and, therefore, upregulate the expression of pro-angiogenic factors as well. Intracellular delivery of siRNA can be achieved with nanocarriers that must fulfill several requirements, including high stability, low toxicity, and high transfection efficiency. Here, we designed and compared the performance of layer-by-layer self-assembled siRNA-loaded gold nanoparticles with two different outer layers—Chitosan (AuNP@CS) and Poly L-arginine (AuNP@PLA). Although both formulations have exactly the same core, we find that a PLA outer layer improves the endosomal escape of siRNA, and therefore, transfection efficiency, after endocytic uptake in NIH-3T3 cells. Furthermore, we found that endosomal escape of AuNP@PLA could be improved further when cells were additionally treated with desloratadine, thus outperforming commercial reagents such as Lipofectamine® and jetPRIME®. AuNP@PLA in combination with desloratadine was proven to induce PHD-2 silencing in fibroblasts, allowing upregulation of pro-angiogenic pathways. This finding in an in vitro context constitutes a first step towards improving diabetic wound healing with siRNA therapy.

Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes

2013 ◽  
Vol 305 (8) ◽  
pp. E951-E963 ◽  
Author(s):  
Milad S. Bitar ◽  
Samy M. Abdel-Halim ◽  
Fahd Al-Mulla
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Cellular Senescence ◽  
Dermal Fibroblasts ◽  
Premature Senescence ◽  
Mrna Levels ◽  
Impaired Wound Healing ◽  
Caveolin 1

A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species, DFs also displayed a significant increase in senescence-associated β-galactosidase activity and phospho-γ-histone H2AX (pH2AX) level. Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes. Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53. This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs. Most of the aforementioned oxidative stress and senescence-based features observed in DFs were recapitulated in a 10-day-old diabetic wound. Intriguingly, we confirmed that the targeted depletion of Cav-1 or PTRF using siRNA- or Vivo-Morpholino antisense-based gene therapy markedly inhibited diabetes/oxidative stress-induced premature senescence and also accelerated tissue repair in this disease state. Overall, our data illuminate Cav-1/PTRF-1 as a key player of a novel signaling pathway that may link a heightened state of oxidative stress to cellular senescence and impaired wound healing in diabetes.

scholarly journals Novel long non-coding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1

2020 ◽  
Author(s):  
Ada Admin ◽  
Mengdie Hu ◽  
Yuxi Wu ◽  
Chuan Yang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Diabetic Foot ◽  
Dermal Fibroblasts ◽  
Diabetic Wound ◽  
Delayed Wound Healing ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. Here, w<a>e identified a novel lncRNA MRAK052872, named lnc-URIDS (lncRNA <u>U</u>p<u>R</u>egulated <u>i</u>n <u>D</u>iabetic <u>S</u>kin), which regulates wound healing in diabetes mellitus. </a>Lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). Lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment <i>in vitro</i> and accelerated diabetic wound healing <i>in vivo</i>. Mechanistically, <a>lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. </a><a>The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. </a><a>The findings of the present study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.</a>

scholarly journals Novel long non-coding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1

2020 ◽  
Author(s):  
Ada Admin ◽  
Mengdie Hu ◽  
Yuxi Wu ◽  
Chuan Yang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Diabetic Foot ◽  
Dermal Fibroblasts ◽  
Diabetic Wound ◽  
Delayed Wound Healing ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. Here, w<a>e identified a novel lncRNA MRAK052872, named lnc-URIDS (lncRNA <u>U</u>p<u>R</u>egulated <u>i</u>n <u>D</u>iabetic <u>S</u>kin), which regulates wound healing in diabetes mellitus. </a>Lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). Lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment <i>in vitro</i> and accelerated diabetic wound healing <i>in vivo</i>. Mechanistically, <a>lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. </a><a>The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. </a><a>The findings of the present study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.</a>

scholarly journals Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yiqiang Hu ◽  
Ranyang Tao ◽  
Lang Chen ◽  
Yuan Xiong ◽  
Hang Xue ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Diabetic Rat ◽  
Diabetic Wound ◽  
Ecm Remodeling ◽  
Diabetic Wound Healing

Abstract Background Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. Results We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. Conclusions PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing. Graphic abstract

scholarly journals Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1445
Author(s):  
Pei-Fang Hsieh ◽  
Cheng-Chia Yu ◽  
Pei-Ming Chu ◽  
Pei-Ling Hsieh
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
High Glucose ◽  
Inhibitory Effect ◽  
Diabetic Patients ◽  
Impaired Wound Healing ◽  
Stress Indicator ◽  
Patients With Diabetes ◽  
Nfκb Pathway ◽  
Oral Wound Healing

Impaired wound healing often occurs in patients with diabetes and causes great inconvenience to them. Aside from the presence of prolonged inflammation, the accumulation of oxidative stress is also implicated in the delayed wound healing. In the present study, we tested the effect of verbascoside, a caffeoyl phenylethanoid glycoside, on the improvement of cell viability and wound healing capacity of gingival epithelial cells under high glucose condition. We showed that verbascoside attenuated the high glucose-induced cytotoxicity and impaired healing, which may be associated with the downregulation of oxidative stress. Our results demonstrated that verbascoside increased the activity of the antioxidant enzyme SOD and reduced the oxidative stress indicator, 8-OHdG, as well as apoptosis. Moreover, verbascoside upregulated the PGC1-α and NRF1 expression and promoted mitochondrial biogenesis, which was mediated by suppression of PKC/HMGB1/RAGE/NFκB signaling. Likewise, we showed the inhibitory effect of verbascoside on oxidative stress was via repression of PKC/HMGB1/RAGE/NFκB activation. Also, our data suggested that the PKC-mediated oxidative stress may lead to the elevated production of inflammatory cytokines, IL-6 and IL-1β. Collectively, we demonstrated that verbascoside may be beneficial to ameliorate impaired oral wound healing for diabetic patients.

Long noncoding RNA OIP5-AS1 overexpression promotes viability and inhibits high glucose-induced oxidative stress of cardiomyocytes by targeting microRNA-34a/SIRT1 axis in diabetic cardiomyopathy

2020 ◽  
Vol 21 ◽  
Author(s):  
Haiyun Sun ◽  
Chong Wang ◽  
Ying Zhou ◽  
Xingbo Cheng
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Promoting Effect

Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes. This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1) on the viability and oxidative stress of cardiomyocyte in DCM. Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells. The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied to analyze the protein expression of SIRT1. Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated. The functional experiment stated that OIP5-AS1 overexpression increased the viability and SOD level, while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the promoting effect on viability, and mitigated the reduction effect on oxidative stress caused by OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells. Conclusions: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for DCM.

A bioglass sustained-release scaffold with ECM-like structure for enhanced diabetic wound healing

Nanomedicine ◽  
2020 ◽  
Vol 15 (23) ◽  
pp. 2241-2253
Author(s):  
Pengju Zhang ◽  
Yuqi Jiang ◽  
Dan Liu ◽  
Yan Liu ◽  
Qinfei Ke ◽  
...  
Keyword(s):  
Wound Healing ◽  
Therapeutic Option ◽  
Effective Strategy ◽  
Diabetic Wound ◽  
Nano Structure ◽  
Wound Site ◽  
Diabetic Wound Healing ◽  
Coaxial Fibers ◽  
Diabetic Wounds ◽  
Endothelial Cell Adhesion

Aim: To develop an effective strategy for increasing angiogenesis at diabetic wound sites and thereby accelerating wound healing. Materials & methods: A micropatterned nanofibrous scaffold with bioglass nanoparticles encapsulated inside coaxial fibers was prepared by electrospinning. Results: Si ions could be released in a sustained manner from the scaffolds. The hierarchical micro-/nano-structure of the scaffold was found to act as a temporary extracellular matrix to promote endothelial cell adhesion and growth. The scaffold greatly improved angiogenesis and collagen deposition at the wound site, which shortened the healing period of diabetic wounds. Conclusion: This study provides a promising therapeutic option for chronic diabetic wounds with improved angiogenesis.

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