scholarly journals Pharmacological PTEN inhibition: potential clinical applications and effects in tissue regeneration

2020 ◽  
Vol 15 (2) ◽  
pp. 1329-1344
Author(s):  
Gabriel A Borges ◽  
Liana P Webber ◽  
Ana Elizia M Marques ◽  
Eliete NS Guerra ◽  
Rogerio M Castilho ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Wounds ◽  
Tissue Injury ◽  
Repair Process ◽  
Healing Time ◽  
Tissue Response ◽  
Phosphatase And Tensin Homolog ◽  
Tissue Repair And Regeneration ◽  
Tensin Homolog ◽  
Pten Inhibition

Although the human body can heal, it takes time, and slow healing and chronic wounds often occur. Thus, identifying novel therapies to aid regeneration is needed. Here, we conducted a systematic review following the Preferred Reporting Items for Systematic Reviews guidelines and assessed preclinical studies on phosphatase and tensin homolog (PTEN) inhibitors and their effects on tissue repair and regeneration. In conditions associated with neurodegeneration, tissue injury and ischemia, the PTEN-regulated PI3K/AKT signaling pathway is activated. The use of PTEN inhibitors resulted in better tissue response by reducing the healing time and lesion sizes or inducing neuronal regeneration. Notably, all studies included in this systematic review indicated that pharmacological inhibition of PTEN enhanced the repair process of the eye, lung, muscle and nervous system.

scholarly journals Adaptive immunity and skin wound healing in amphibian adults

2019 ◽  
Vol 14 (1) ◽  
pp. 420-426 ◽  
Author(s):  
Antonella Franchini
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Skin Wound ◽  
Tissue Response ◽  
Cellular Mechanisms ◽  
Skin Wound Healing ◽  
Whole Process ◽  
Tissue Repair And Regeneration ◽  
Adaptive Immune Cells

AbstractRegeneration and repair with scarring of the skin are two different responses to tissue injury that proceed depending on the animal species. Several studies in multiple organisms have shown that the effectiveness of tissue repair gradually decreases with age in most vertebrates, while the molecular and cellular mechanisms underlying the diverse potentials remain incompletely understood. It is clear, however, that immune system actively participates in the whole process and immune-related activities can mediate both negative and positive roles to influence the quality and diversity of tissue response to damage. Compared with innate immunity, our understanding of the significance of adaptive immune cells in normal repair outcome is limited and deserves further investigation. Here, experimental evidence supporting the contribution of lymphocytes and the involvement of lymphoid organs in skin wound healing are discussed, focusing on the findings emerged in adult amphibians, key animal models for tissue repair and regeneration research.

Efficacy of MMP-inhibiting wound dressings in the treatment of chronic wounds: a systematic review

2020 ◽  
Vol 29 (2) ◽  
pp. 102-118 ◽  
Author(s):  
Joachim Dissemond ◽  
Matthias Augustin ◽  
Michael Dietlein ◽  
Uta Faust ◽  
Winfried Keuthage ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Closure ◽  
Clinical Evidence ◽  
Chronic Wounds ◽  
Evidence Base ◽  
Healing Time ◽  
Size Reduction ◽  
Wound Dressings ◽  
Wound Size ◽  
Different Types

Objective: Matrix metalloproteinases (MMPs) substantially contribute to the development of chronicity in wounds. Thus, MMP-inhibiting dressings may support healing. A systematic review was performed to determine the existing evidence base for the treatment of hard-to-heal wounds with these dressings. Methods: A systematic literature search in databases and clinical trial registers was conducted to identify randomised controlled trials (RCTs) investigating the efficacy of MMP-inhibiting dressings. Studies were analysed regarding their quality and clinical evidence. Results: Of 721 hits, 16 relevant studies were assessed. There were 13 studies performed with collagen and three with technology lipido-colloid nano oligosaccharide factor (TLC-NOSF) dressings. Indications included diabetic foot ulcers, venous leg ulcers, pressure ulcers or wounds of mixed origin. Patient-relevant endpoints comprised wound size reduction, complete wound closure, healing time and rate. Considerable differences in the quality and subsequent clinical evidence exist between the studies identified. Substantial evidence for significant improvement in healing was identified only for some dressings. Conclusion: Evidence for the superiority of some MMP-inhibiting wound dressings exists regarding wound closure, wound size reduction, healing time and healing rate. More research is required to substantiate the existing evidence for different types of hard-to-heal wounds and to generate evidence for some of the different types of MMP-inhibiting wound dressings.

scholarly journals Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Inhibition by 4-Hydroxynonenal Leads to Increased Akt Activation in Hepatocytes

2011 ◽  
Vol 79 (6) ◽  
pp. 941-952 ◽  
Author(s):  
Colin T. Shearn ◽  
Rebecca L. Smathers ◽  
Benjamin J. Stewart ◽  
Kristofer S. Fritz ◽  
James J. Galligan ◽  
...  
Keyword(s):  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Akt Activation ◽  
Tensin Homolog ◽  
Pten Inhibition

scholarly journals Involvement of the PTEN–AKT–FOXO3a Pathway in Neuronal Apoptosis in Developing Rat Brain after Hypoxia–Ischemia

2009 ◽  
Vol 29 (12) ◽  
pp. 1903-1913 ◽  
Author(s):  
Deyuan Li ◽  
Yi Qu ◽  
Meng Mao ◽  
Xiaolan Zhang ◽  
Jinhui Li ◽  
...  
Keyword(s):  
Rat Brain ◽  
Neuronal Apoptosis ◽  
Nuclear Translocation ◽  
Neonatal Rat ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Hypoxia Ischemia ◽  
Cellular Apoptosis ◽  
Pten Inhibition ◽  
Developing Rat

The proapoptotic function of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphatase has been linked to its capacity to antagonize the phosphatidylinositol-3-kinase–Akt signaling pathway. Previous studies have shown that the Forkhead transcriptional factor (FOXO3a) is a critical effector of the PTEN-mediated tumor suppressor. However, whether the PTEN–Akt–FOXO3a pathway is involved in neuronal apoptosis in developing rat brain after hypoxia–ischemia (HI) is unclear. In this study, we generated an HI model using postnatal day 10 rats. Immunohistochemistry and western blot were used to detect the expression of total and phosphorylated PTEN, Akt, and FOXO3a, as well as its target gene Bim. We found that dephosphorylation of PTEN was accompanied by dephosphorylation of Akt and FOXO3a, which induced FOXO3a translocation into the nucleus and upregulated the expression of Bim. Furthermore, we found that PTEN inhibition by bisperoxovanadium significantly increased the phosphorylation of Akt and FOXO3a, decreased the nuclear translocation of FOXO3a, and inhibited Bim expression after HI. Moreover, the downregulation of Bim caused by PTEN inhibition attenuated cellular apoptosis in developing rat brain. Our findings suggest that the PTEN–Akt–FOXO3a pathway is involved in neuronal apoptosis in neonatal rat brain after HI. Agents targeting PTEN may offer a promise to rescue neurons from HI brain damage.

scholarly journals High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)

2020 ◽  
Vol 40 (8) ◽  
pp. 1854-1869
Author(s):  
Keith A. Strand ◽  
Sizhao Lu ◽  
Marie F. Mutryn ◽  
Linfeng Li ◽  
Qiong Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
High Throughput ◽  
Knockout Mice ◽  
Vascular Remodeling ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Protective Effects ◽  
High Throughput Screen ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

miR-139-5p promotes neovascularization in diabetic retinopathy by regulating the phosphatase and tensin homolog

2021 ◽  
Vol 44 (2) ◽  
pp. 205-218
Author(s):  
Zhongwei Zhang ◽  
Caiping Song ◽  
Tao Wang ◽  
Lei Sun ◽  
Ling Qin ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog
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