Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia

Peng, Zhiyou; Qin, Jining; Ye, Kaichuang; Wang, Xin; Shi, Huigang; Jiang, Mier; Liu, Xiaobing; Lu, Xinwu

doi:10.5966/sctm.2015-0380

Cited by 41 publications

(39 citation statements)

References 34 publications

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“…For DM, longterm hyperglycaemic exposure of ASC and ECM influences their biological properties (Haucke, Navarrete-Santos, Simm, Silber, & Hofmann, 2014;Serban et al, 2015;Voziyan, Brown, Chetyrkin, & Hudson, 2014). High levels of glucose impair the regenerative function of ASC by intracellular reactive oxygen species accumulation (Peng et al, 2017). Reactive oxygen species inhibits the proliferation and proangiogenic capacities of ASC, which are important processes in wound healing (Peng et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue‐derived extracellular matrix hydrogels as a release platform for secreted paracrine factors

Dongen

Getova

Brouwer

et al. 2019

J Tissue Eng Regen Med

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Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue‐derived ECM hydrogels as release platform for factors secreted by adipose‐derived stromal cells (ASCs). Lipoaspirates from nondiabetic and diabetic donors were decellularized. Finely powdered acellular ECM was evaluated for cell remainders and DNA content. Acellular ECM was digested, and hydrogels were formed at 37°C and their viscoelastic relaxation properties investigated. Release of ASC‐released factors from hydrogels was immune assessed, and bio‐activity was determined by fibroblast proliferation and migration and endothelial angiogenesis. Acellular ECM contained no detectable cell remainders and negligible DNA contents. Viscoelastic relaxation measurements yielded no data for diabetic‐derived hydrogels due to gel instability. Hydrogels released several ASC‐released factors concurrently in a sustained fashion. Functionally, released factors stimulated fibroblast proliferation and migration as well as angiogenesis. No difference between nondiabetic and diabetic hydrogels in release of factors was measured. Adipose ECM hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing‐related processes by releasing factors in a controlled way.

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Section: Introductionmentioning

confidence: 99%

Adipose tissue‐derived extracellular matrix hydrogels as a release platform for secreted paracrine factors

Dongen

Getova

Brouwer

et al. 2019

J Tissue Eng Regen Med

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“…ADSCs and N-ADSCs were incubated in high-glucose condition for 48 h. The rate of apoptosis was analyzed with the Annexin V apoptosis detection kit (BD Bioscience, New York, USA) as described previously [ 11 ]. After incubation, we harvested the floating and adherent cells by trypsinization and used Annexin V (Thermo Fisher) and propidium iodide (PI) to stain the cells for 15 min, followed by flow cytometry (Beckman Coulter) to quantify the percentage of apoptotic cells (Annexin V + /PI − ).…”

Section: Methodsmentioning

confidence: 99%

Netrin-1 improves adipose-derived stem cell proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation

et al. 2018

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BackgroundDiabetic peripheral neurovascular diseases (DPNVs) are complex, lacking effective treatment. Autologous/allogeneic transplantation of adipose-derived stem cells (ADSCs) is a promising strategy for DPNVs. Nonetheless, the transplanted ADSCs demonstrate unsatisfying viability, migration, adhesion, and differentiation in vivo, which reduce the treatment efficiency. Netrin-1 secreted as an axon guidance molecule and served as an angiogenic factor, demonstrating its ability in enhancing cell proliferation, migration, adhesion, and neovascularization.MethodsADSCs acquired from adipose tissue were modified by Netrin-1 gene (NTN-1) using the adenovirus method (N-ADSCs) and proliferation, migration, adhesion, and apoptosis examined under high-glucose condition. The sciatic denervated mice (db/db) with type 2 diabetes mellitus (T2DM) were transplanted with N-ADSCs and treatment efficiency assessed based on the laser Doppler perfusion index, immunofluorescence, and histopathological assay. Also, the molecular mechanisms underlying Netrin-1-mediated proliferation, migration, adhesion, differentiation, proangiogenic capacity, and apoptosis of ADSCs were explored.ResultsN-ADSCs improved the proliferation, migration, and adhesion and inhibited the apoptosis of ADSCs in vitro in the condition of high glucose. The N-ADSCs group demonstrated an elevated laser Doppler perfusion index in the ADSCs and control groups. N-ADSCs analyzed by immunofluorescence and histopathological staining demonstrated the distribution of the cells in the injected limb muscles, indicating chronic ischemia; capillaries and endothelium were formed by differentiation of N-ADSCs. The N-ADSCs group showed a significantly high density of the microvessels than the ADSCs group. The upregulation of AKT/PI3K/eNOS/P-38/NF-κB signaling pathways and secretion of multiple growth factors might explain the positive effects of Netrin-1 on ADSCs.ConclusionThe overexpression of Netrin-1 in ADSCs improves proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation, which directs the clinical treatment of patients with DPNVs.

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“…Reduced glutathione (GSH), a cofactor required by Glo-1 to clear MG, is a main product of γ-glutamylcysteine synthetase (γ-GCS), which is regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Mounting evidence suggests that Glo-1 overexpression has a therapeutic effect on diabetic complications ( Maher et al., 2011 ; Liu et al., 2017b ; Peng et al., 2017 ), including diabetic encephalopathy ( Liu et al., 2013a ; Zhu et al., 2018 ). MG formation and decreased Glo-1 function play crucial roles in the metabolism of chronic hyperglycemia ( Thornalley, 1994 ); therefore, the induction or enhancement of Glo-1 is considered to be an important strategy for the prevention and treatment of common diabetic complications, such as depression.…”

Section: Introductionmentioning

confidence: 99%

The Antidepressant-Like Effects of Hesperidin in Streptozotocin‐Induced Diabetic Rats by Activating Nrf2/ARE/Glyoxalase 1 Pathway

Zhu

Liu

et al. 2020

Front. Pharmacol.

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The co-occurrence of diabetes and depression is a challenging and underrecognized clinical problem. Alpha-carbonyl aldehydes and their detoxifying enzyme glyoxalase 1 (Glo-1) play vital roles in the pathogenesis of diabetic complications, including depression. Hesperidin, a naturally occurring flavanone glycoside, possesses numerous pharmacological properties, but neuroprotection by hesperidin in depression-like behaviors in diabetes was not observed. This study aimed to investigate the mechanisms and signaling pathways by which hesperidin regulates depression-like behaviors in diabetic rats and to identify potential targets of hesperidin. Rats with streptozotocin-induced diabetes were treated orally with hesperidin (50 and 150 mg/kg) or the nuclear factor erythroid 2-related factor 2 (Nrf2) inducer tert-butylhydroquinone (TBHQ, 25 mg/kg) for 10 weeks. After behavioral test, the brains were collected to evaluate the effects of hesperidin on Glo-1, Nrf2, protein glycation, and oxidative stress. Hesperidin showed antidepressant and anxiolytic effects in diabetic rats, as evidenced by the decreased immobility time in the forced swimming test, increased time spent in the center area of the open field test, and increased percentage of open-arm entries and time spent in the open arms in the elevated plus maze, as well as by the enhancement of Glo-1 and the inhibition of the AGEs/RAGE axis and oxidative stress in the brain. In addition, hesperidin caused significant increases in the Nrf2 levels and upregulated γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling. In vitro , the effects of hesperidin on N2a cell injury caused by high glucose (HG) was assessed by MTT and LDH, and the effects on Nrf2 signaling were also assessed. We found that the Nrf2 inhibitor ML385 reversed the protective effects of hesperidin on the cell injury induced by HG. Hesperidin prevented the HG-induced reduction in the Nrf2 and Glo-1 levels, and ML385 reversed the effects of hesperidin on the expression of the proteins mentioned above, indicating that Nrf2 signaling is involved in the hesperidin-induced neuroprotective effects. Our findings indicate that the effects of hesperidin on ameliorating the depression- and anxiety-like behaviors of diabetic rats, which are mediated by the enhancement of Glo-1, may be due to the activation of the Nrf2/ARE pathway.

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Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia

Cited by 41 publications

References 34 publications

Adipose tissue‐derived extracellular matrix hydrogels as a release platform for secreted paracrine factors

Adipose tissue‐derived extracellular matrix hydrogels as a release platform for secreted paracrine factors

Netrin-1 improves adipose-derived stem cell proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation

The Antidepressant-Like Effects of Hesperidin in Streptozotocin‐Induced Diabetic Rats by Activating Nrf2/ARE/Glyoxalase 1 Pathway

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