World Journal of Diabetes最新文献

{"title":"O-linked β-N-acetylglucosamine transferase regulates macrophage polarization in diabetic periodontitis: <i>In vivo</i> and <i>in vitro</i> study.","authors":"Ye-Ke Wu, Min Liu, Hong-Ling Zhou, Xiang He, Jing Wei, Wei-Han Hua, Hui-Jing Li, Qiang-Hua Yuan, Yun-Fei Xie","doi":"10.4239/wjd.v16.i3.95092","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.95092","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis, when exacerbated by diabetes, is characterized by increased M1 macrophage polarization and decreased M2 polarization. O-linked β-N-acetylglucosamine (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), promotes inflammatory responses in diabetic periodontitis (DP). Additionally, p38 mitogen-activated protein kinase regulates macrophage polarization. However, the interplay between OGT, macrophage polarization, and p38 signaling in the progression of DP remains unexplored.</p><p><strong>Aim: </strong>To investigate the effect of OGT on macrophage polarization in DP and its role in mediating O-GlcNAcylation of p38.</p><p><strong>Methods: </strong>For <i>in vivo</i> experiments, mice were divided into four groups: Control, DP model, model + short hairpin (sh) RNA-negative control, and model + sh-OGT. Diabetes was induced by streptozotocin, followed by ligation and lipopolysaccharide (LPS) administration to induce periodontitis. The impact of OGT was assessed by injecting sh-OGT lentivirus. Maxillary bone destruction was evaluated using micro-computed tomography analysis and tartrate-resistant acid phosphatase staining, while macrophage polarization was determined through quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry. For <i>in vitro</i> experiments, RAW264.7 cells were treated with LPS and high glucose (HG) (25 mmol/L D-glucose) to establish a cell model of DP. OGT was inhibited by OGT inhibitor (OSMI4) treatment and knocked down by sh-OGT transfection. M1/M2 polarization was analyzed using qPCR, immunofluorescence, and flow cytometry. Levels of O-GlcNAcylation were measured using immunoprecipitation and western blotting.</p><p><strong>Results: </strong>Our results demonstrated that M1 macrophage polarization led to maxillary bone loss in DP mice, associated with elevated O-GlcNAcylation and OGT levels. Knockdown of OGT promoted the shift from M1 to M2 macrophage polarization in both mouse periodontal tissues and LPS + HG-induced RAW264.7 cells. Furthermore, LPS + HG enhanced the O-GlcNAcylation of p38 in RAW264.7 cells. OGT interacted with p38 to promote its O-GlcNAcylation at residues A28, T241, and T347, as well as its phosphorylation at residue Y221.</p><p><strong>Conclusion: </strong>Inhibition of OGT-mediated p38 O-GlcNAcylation deactivates the p38 pathway by suppressing its self-phosphorylation, thereby promoting M1 to M2 macrophage polarization and mitigating DP. These findings suggested that modulating macrophage polarization through regulation of O-GlcNAcylation may represent a novel therapeutic strategy for treating DP.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"95092"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glabridin and gymnemic acid alleviates choroid structural change and choriocapillaris impairment in diabetic rat's eyes.","authors":"Udomlak Matsathit, Manaras Komolkriengkrai, Wipapan Khimmaktong","doi":"10.4239/wjd.v16.i3.97336","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.97336","url":null,"abstract":"<p><strong>Background: </strong>Small blood vessels in the eyes are more susceptible to injury, which can lead to complications. However, since diabetic retinopathy is often a serious clinical condition, most of this study focuses on the vascular system of the choroid. As part of this study, we looked at how gymnemic acid (from <i>Gymnema sylvestre</i>) and glabridin (from <i>Glycyrrhiza glabra</i>, or licorice) might help diabetic rats' choroid structural change and blood vessels.</p><p><strong>Aim: </strong>To explore the effects of glabridin and gymnemic acid on the structural changes of the choroidal layer and choriocapillaris as well as the expression of vascular endothelial growth factor (VEGF) and cluster of differentiation (CD) 31 in diabetic rat's eye.</p><p><strong>Methods: </strong>The male Wistar rats were separated into five groups: The control group (control), the diabetic group (DM), the diabetic rats treated with glabridin 40 mg/kg body weight (DM + GB), the diabetic rats treated with gymnemic acid 400 mg/kg body weight (DM + GM), and the diabetic rats treated with glyburide 4 mg/kg body weight (DM + GR).</p><p><strong>Results: </strong>There was an increase in the thickness of both the choroid layer and the wall of the arteries in the DM. A decrease in vascularity and choroidal impairment was found in DM rats. After eight weeks of experimentation, the choroidal thickness increased, and the walls of choroid arteries. The choroidal thickness in the DM + GB was 15.69 ± 1.54 μm, DM + GM was 14.84 ± 1.31, and DM + GR groups was 16.45 ± 1.15 when compared with DM group (27.22 ± 2.05), the walls thickness of choroid arteries in the DM + GB was 10.23 ± 1.11, DM + GM was 10.41 ± 1.44, and DM + GR was 9.80 ± 1.78 when compared with DM group (16.35 ± 5.01), The expression of VEGF and CD31 was lower compared to the DM group.</p><p><strong>Conclusion: </strong>In diabetic choroidopathy, hyperglycemia and inflammation cause damage to the neurovascular unit and blood-retinal barrier. Anti-VEGF treatments can slow or reverse the progression of the disease. According to current research findings, glabridin and gymnemic acid can reduce damage to the choroid, which is a factor that can sometimes result in vision loss.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"97336"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and a predictive model of diabetic foot in hospitalized patients with type 2 diabetes.","authors":"Ming-Zhuo Li, Fang Tang, Ya-Fei Liu, Jia-Hui Lao, Yang Yang, Jia Cao, Ru Song, Peng Wu, Yi-Bing Wang","doi":"10.4239/wjd.v16.i3.95644","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.95644","url":null,"abstract":"<p><strong>Background: </strong>The risk factors and prediction models for diabetic foot (DF) remain incompletely understood, with several potential factors still requiring in-depth investigations.</p><p><strong>Aim: </strong>To identify risk factors for new-onset DF and develop a robust prediction model for hospitalized patients with type 2 diabetes.</p><p><strong>Methods: </strong>We included 6301 hospitalized patients with type 2 diabetes from January 2016 to December 2021. A univariate Cox model and least absolute shrinkage and selection operator analyses were applied to select the appropriate predictors. Nonlinear associations between continuous variables and the risk of DF were explored using restricted cubic spline functions. The Cox model was further employed to evaluate the impact of risk factors on DF. The area under the curve (AUC) was measured to evaluate the accuracy of the prediction model.</p><p><strong>Results: </strong>Seventy-five diabetic inpatients experienced DF. The incidence density of DF was 4.5/1000 person-years. A long duration of diabetes, lower extremity arterial disease, lower serum albumin, fasting plasma glucose (FPG), and diabetic nephropathy were independently associated with DF. Among these risk factors, the serum albumin concentration was inversely associated with DF, with a hazard ratio (HR) and 95% confidence interval (CI) of 0.91 (0.88-0.95) (<i>P</i> < 0.001). Additionally, a <i>U</i>-shaped nonlinear relationship was observed between the FPG level and DF. After adjusting for other variables, the HRs and 95%CI for FPG < 4.4 mmol/L and ≥ 7.0 mmol/L were 3.99 (1.55-10.25) (<i>P</i> = 0.004) and 3.12 (1.66-5.87) (<i>P</i> < 0.001), respectively, which was greater than the mid-range level (4.4-6.9 mmol/L). The AUC for predicting DF over 3 years was 0.797.</p><p><strong>Conclusion: </strong>FPG demonstrated a <i>U</i>-shaped relationship with DF. Serum albumin levels were negatively associated with DF. The prediction nomogram model of DF showed good discrimination ability using diabetes duration, lower extremity arterial disease, serum albumin, FPG, and diabetic nephropathy (Clinicaltrial.gov NCT05519163).</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"95644"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LEF1 influences diabetic retinopathy and retinal pigment epithelial cell ferroptosis <i>via</i> the <i>miR-495-3p/GRP78</i> axis through <i>lnc-MGC</i>.","authors":"Yi-Yi Luo, Xue-Ying Ba, Ling Wang, Ye-Pin Zhang, Hong Xu, Pei-Qi Chen, Li-Bo Zhang, Jian Han, Heng Luo","doi":"10.4239/wjd.v16.i3.92003","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.92003","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is one of the major eye diseases contributing to blindness worldwide. Endoplasmic reticulum (ER) stress in retinal cells is a key factor leading to retinal inflammation and vascular leakage in DR, but its mechanism is still unclear.</p><p><strong>Aim: </strong>To investigate the potential mechanism of LEF1 and related RNAs in DR.</p><p><strong>Methods: </strong>ARPE-19 cells were exposed to high levels of glucose for 24 hours to simulate a diabetic environment. Intraperitoneally injected streptozotocin was used to induce the rat model of DR. The expression levels of genes and related proteins were measured by RT-qPCR and Western blotting; <i>lnc-MGC</i> and <i>miR-495-3p</i> were detected by fluorescent <i>in situ</i> hybridization; CCK-8 and TUNEL assays were used to detect cell viability and apoptosis; enzyme-linked immunosorbent assay was used to detect inflammatory factors; dual-luciferase gene assays were used to verify the targeting relationship; and the retina was observed by HE staining.</p><p><strong>Results: </strong>LEF1 and <i>lnc-MGC</i> have binding sites, and <i>lnc-MGC</i> can regulate the <i>miR-495-3p</i>/<i>GRP78</i> molecular axis. In high glucose-treated cells, inflammation was aggravated, the intracellular reactive oxygen species concentration was increased, cell viability was reduced, apoptosis was increased, the ER response was intensified, and ferroptosis was increased. As an ER molecular chaperone, GRP78 regulates the ER and ferroptosis under the targeting of <i>miR-495-3p</i>, whereas inhibiting <i>LEF1</i> can further downregulate the expression of <i>lnc-MGC</i>, increase the level of <i>miR-495-3p</i>, and sequentially regulate the level of GRP78 to alleviate the occurrence and development of DR. Animal experiments indicated that the knockdown of LEF1 can affect the <i>lnc-MGC</i>/<i>miR-495-3p</i>/<i>GRP78</i> signaling axis to restrain the progression of DR.</p><p><strong>Conclusion: </strong><i>LEF1</i> knockdown can regulate the <i>miR-495-3p</i>/<i>GRP78</i> molecular axis through <i>lnc-MGC</i>, which affects ER stress and restrains the progression of DR and ferroptosis in retinal pigment epithelial cells.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"92003"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical characteristics of chronic kidney disease among patients with newly diagnosed ketosis-onset diabetes.","authors":"Meng-Han Li, Man-Rong Xu, Yu-Jie Wang, Li Shen, Ming-Yun Chen, Lian-Xi Li","doi":"10.4239/wjd.v16.i3.100059","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.100059","url":null,"abstract":"<p><strong>Background: </strong>The prevalence and clinical characteristics of chronic kidney disease (CKD) among patients with ketosis-onset diabetes (also known as ketosis-prone diabetes) remain unclear. Furthermore, the classification of ketosis-onset diabetes remains controversial and requires further investigation.</p><p><strong>Aim: </strong>To investigate the prevalence and clinical features of CKD in patients with newly diagnosed ketosis-onset diabetes.</p><p><strong>Methods: </strong>This real-world study included 217 patients with type 1 diabetes mellitus (T1DM), 698 with ketosis-onset diabetes, and 993 with non-ketotic T2DM. The prevalence and clinical characteristics of CKD were compared among the three groups. Risk factors associated with CKD were evaluated using binary logistic regression for each group.</p><p><strong>Results: </strong>After adjusting for age and sex, the prevalence of CKD among patients with ketosis-onset diabetes (17.8%) was significantly higher than that in those with T1DM (8.3%, <i>P</i> = 0.007), but was not statistically different compared to those with non-ketotic T2DM (21.7%, <i>P</i> = 0.214). Furthermore, some risk factors for CKD, including age, and serum uric acid and C-reactive protein levels, in patients with ketosis-onset diabetes were similar to those with T2DM, but significantly different from those with T1DM.</p><p><strong>Conclusion: </strong>The prevalence, clinical characteristics, and risk factors for CKD among patients with ketosis-onset diabetes were more similar to those with non-ketotic T2DM but considerably different from those with T1DM. These findings further support the classification of ketosis-onset diabetes as a subtype of T2DM rather than idiopathic T1DM.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"100059"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive review on diabetic foot ulcers and neuropathy: Treatment, prevention and management.","authors":"Kehkashan Parveen, Malik Asif Hussain, Sadaf Anwar, Halima Mustafa Elagib, Mohd Adnan Kausar","doi":"10.4239/wjd.v16.i3.100329","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.100329","url":null,"abstract":"<p><p>Diabetic foot (DF) is a major public health concern. As evident from numerous previous studies, supervision of DF ulcer (DFU) is crucial, and a specific quality check-up is needed. Patients should be educated about glycaemic management, DFUs, foot lesions, proper care for injuries, diet, and surgery. Certain reasonably priced treatments, such as hyperbaric oxygen and vacuum-assisted closure therapy, are also available for DFUs, along with modern wound care products and techniques. Nonetheless, DF care (cleaning, applying antimicrobial cream when wounded, and foot reflexology), blood glucose monitoring to control diabetes, and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs. Between 50% and 80% of DF infections are preventable. Regardless of the intensity of the lesion, it needs to be treated carefully and checked daily during infection. Tissue regeneration can be aided by cleaning, dressing, and application of topical medicines. The choice of shoes is also important because it affects blood circulation and nerve impulses. In general, regular check-ups, monitoring of the patient's condition, measuring blood glucose levels, and providing frequent guidance regarding DFU care are crucial. Finally, this important clinical problem requires involvement of multiple professionals to properly manage it.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"100329"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing dialysis modalities for diabetic end-stage kidney disease: A focus on personalized care and resource-limited settings.","authors":"Arun Prabhahar, Akshey Batta, Juniali Hatwal, Vivek Kumar, Raja Ramachandran, Akash Batta","doi":"10.4239/wjd.v16.i3.100592","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.100592","url":null,"abstract":"<p><p>Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. While both haemodialysis (HD) and peritoneal dialysis (PD) are commonly used treatment options for ESKD, the choice of dialysis modality in diabetic ESKD patients remains a critical decision influenced by various patient-related, healthcare system, and socio-economic factors. This article examines the factors influencing the selection of dialysis modalities for diabetic patients, with a focus on the challenges and opportunities in low-resource settings. Key considerations include the impact of comorbidities such as peripheral arterial disease and CKD-related mineral bone disorder (MBD), as well as patient preferences, caregiver burden, and the availability of healthcare infrastructure. The article highlights the need for personalized approaches to dialysis selection, considering both clinical outcomes and quality of life. It also emphasizes the potential benefits of home dialysis, including home HD and PD, in improving patient autonomy and long-term survival. The article advocates for better government policies, increased awareness, and improved support systems to enhance the accessibility and efficacy of dialysis treatments, particularly in underserved populations. Further research comparing the outcomes of different dialysis modalities across diverse settings is essential to guide global treatment strategies for diabetic ESKD patients.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"100592"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture relieves type 2 diabetes by regulating gut microbiome.","authors":"Ya-Jing Yang, Xu-Chang Zhou, Hao-Ran Tian, Feng-Xia Liang","doi":"10.4239/wjd.v16.i3.103032","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.103032","url":null,"abstract":"<p><p>Cumulative studies have shown that the composition of the gut microbiome is strongly associated with the development of type 2 diabetes mellitus (T2DM). Electroacupuncture (EA) therapy has been reported to alleviate various diseases, including T2DM, by targeting specific acupuncture points and regulating metabolic homeostasis. A recent review published in the <i>World Journal of Diabetes</i> detailed the role of the gut microbiome in T2DM, discussing the role of therapeutic strategies developed to alleviate T2DM and its complications based on gut microbiome in ameliorating T2DM, as well as the effects of multiple diabetes medications on gut microbiome. However, the review did not elucidate the therapeutic role of EA therapy, a common non-pharmacological intervention for T2DM. This letter complemented the effect of EA therapy on glucose metabolism by adjusting the gut microbiome composition, which reveals the underlying mechanism of glucose lowering by EA therapy and provides a scientific basis for the application of EA therapy in clinical treatment.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"103032"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From metabolic regulation to kidney protection: β-arrestin 2 as a dual-function therapeutic target.","authors":"Jian Yang, Cheng-Zhi Zhang, Jing Zhang","doi":"10.4239/wjd.v16.i3.102014","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.102014","url":null,"abstract":"<p><p>We are deeply interested in the recent findings on β-arrestin 2. Liu <i>et al</i> demonstrated that β-arrestin 2 knockout provides significant protection in diabetic nephropathy, underscoring its potential as a promising therapeutic target for diabetic nephropathy treatment. Furthermore, the role of β-arrestin 2 in metabolic regulation is equally critical, particularly in insulin signaling, hepatic glucose production, and adipose tissue function. Although β-arrestin 2 plays a distinct role in metabolism and kidney protection, its tissue-specific regulation opens up valuable avenues for developing targeted therapeutic strategies centered on β-arrestin 2.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"102014"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through epigenetically activating DNA methyltransferase 1.","authors":"Ren-Jie Xiao, Tian-Jiao Wang, Dan-Yin Wu, Shui-Fa Yang, Hai Gao, Pei-Dong Gan, Yang-Yan Yi, You-Lai Zhang","doi":"10.4239/wjd.v16.i3.102126","DOIUrl":"https://doi.org/10.4239/wjd.v16.i3.102126","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wound injury is a significant and common complication in individuals with diabetes. N6-methyladenosine (m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complications. However, the function of m6A methyltransferase Wilms tumor 1-associated protein (WTAP) in diabetic wound healing remains elusive.</p><p><strong>Aim: </strong>To investigate the potential epigenetic regulatory mechanism of WTAP during diabetic wound healing.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) were induced with high glucose (HG) to establish <i>in vitro</i> cell model. Male BALB/c mice were intraperitoneally injected with streptozotocin to mimic diabetes, and full-thickness excision was made to mimic diabetic wound healing. HG-induced HUVECs and mouse models were treated with WTAP siRNAs and DNA methyltransferase 1 (DNMT1) overexpression vectors. Cell viability and migration ability were detected by cell counting kit-8 and Transwell assays. <i>In vitro</i> angiogenesis was measured using a tube formation experiment. The images of wounds were captured, and re-epithelialization and collagen deposition of skin tissues were analyzed using hematoxylin and eosin staining and Masson's trichrome staining.</p><p><strong>Results: </strong>The expression of several m6A methyltransferases, including METTL3, METTL14, METTL16, KIAA1429, WTAP, and RBM15, were measured. WTAP exhibited the most significant elevation in HG-induced HUVECs compared with the normal control. WTAP depletion notably restored cell viability and enhanced tube formation ability and migration of HUVECs suppressed by HG. The unclosed wound area of mice was smaller in WTAP knockdown-treated mice than in control mice at nine days post-wounding, along with enhanced re-epithelialization rate and collagen deposition. The m6A levels on DNMT1 mRNA in HUVECs were repressed by WTAP knockdown in HUVECs. The mRNA levels and expression of DNMT1 were inhibited by WTAP depletion in HUVECs. Overexpression of DNMT1 in HUVECs notably reversed the effects of WTAP depletion on HG-induced HUVECs.</p><p><strong>Conclusion: </strong>WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNMT1 to impair diabetic wound healing.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 3","pages":"102126"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}