Protein and Peptide Letters最新文献

{"title":"Immunity in Harmony: Utilizing Overlapping Epitopes for Tuberculosis and COVID-19 Protection.","authors":"Kritika Pasricha, Shivank Prajapati, Taruna Lamba, Jonaid Ahmad Malik, Mohd Affan Khan, Sidhanta Nanda, Mohammad Adeel Zafar, Nitesh Mani Tripathi, Anupam Bandyopadhyay, Javed Naim Agrewala","doi":"10.2174/0109298665417756251207111117","DOIUrl":"https://doi.org/10.2174/0109298665417756251207111117","url":null,"abstract":"<p><strong>Introduction: </strong>The BCG vaccine, widely administered against tuberculosis, has also been linked to reduced incidence of bacterial and viral infections, particularly those affecting the respiratory tract. Its antigens enhance innate immune responses and contribute to therapeutic effects, such as those observed in bladder cancer. Notably, reduced COVID-19 incidence has been reported in BCG-vaccinated populations from TB-endemic regions.</p><p><strong>Methods: </strong>To investigate this hypothesis, immunoinformatics tools were employed to identify overlapping CD4, CD8, and B-cell epitopes shared between Mycobacteria and SARS-CoV-2. The most promising CD8 epitope was synthesized using the SPPS-Fmoc method, and antigen-specific Tcell proliferation was evaluated by CFSE dye-dilution assay. Additionally, the expression of proand anti-inflammatory molecules was assessed using qRT-PCR.</p><p><strong>Results: </strong>Multiple overlapping T-cell and B-cell epitopes were identified between Mycobacteria and SARS-CoV-2. The T-cell epitopes displayed promiscuous binding characteristics, high immunogenicity, and strong affinity for both HLA class I and class II alleles. Experimental validation using the most immunodominant T-cell epitope confirmed its ability to induce proliferation and differentiation of T cells isolated from COVID-19-vaccinated individuals.</p><p><strong>Discussion: </strong>The overlapping T-cell and B-cell epitopes identified through this approach may provide broader and more robust protection than initial exposure to virus-specific antigens, which the immune system encounters for the first time during infection or vaccination. This strategy may therefore support the rapid and effective development of future vaccines, particularly against emerging pathogens.</p><p><strong>Conclusion: </strong>The findings suggest that the higher level of protection observed in TB-endemic countries during recent pandemics may be attributable to cross-reactive mycobacterial antigens that stimulate protective immunity.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Nature of Venom: Transforming Toxins into Therapeutic Peptides.","authors":"Chloe Zi En Wong, Wei Hsum Yap, Adeline Yoke Yin Chia, Yin-Quan Tang","doi":"10.2174/0109298665429958251204082928","DOIUrl":"https://doi.org/10.2174/0109298665429958251204082928","url":null,"abstract":"<p><p>Venom has been extracted from venomous animals since ancient times for use as hunting tools or biological weapons. In the modern era, the focus has shifted toward the biomedical potential of venom, particularly its rich composition of bioactive compounds. Among these, venom peptides are of particular interest due to their potent and selective biological activities. These peptides often constitute a significant portion of crude venom mixtures and have emerged as promising candidates for drug development. The growing body of research in this field has led to the establishment of \"venomics,\" a discipline that integrates proteomics, transcriptomics, and genomics to comprehensively characterize venom components. Technological advancements, such as high-throughput sequencing, mass spectrometry, and advanced computational tools, have revolutionized venomics, enabling deeper insights into venom composition, function, and evolutionary biology. These innovations have facilitated the discovery of venom-derived peptides with therapeutic applications, including treatments for chronic pain, cancer, cardiovascular diseases, and autoimmune disorders. However, despite these promising developments, challenges remain. These include the complexity of venom mixtures, ethical considerations in venom collection, and difficulties in translating in vitro findings into clinical applications. This review explores the evolution and technological progress of venomics, highlights key therapeutic applications of venom peptides, and discusses current limitations and future prospects in the field.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin Mitigates Myocardial Hypoxia/Reoxygenation Injury by Preserving Mitochondrial Redox Homeostasis via the UCP2-SOD2 Axis.","authors":"Yizhen Xu, Huanqing Liu, Shuang Liu, Peng Wu, Rui Wang, You Li, Xiaona Wang, Qiuyu Cao, Lei Duan, Ruobai Qiao, Hao Tang, Zhen Wang","doi":"10.2174/0109298665445300260128064859","DOIUrl":"https://doi.org/10.2174/0109298665445300260128064859","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial redox homeostasis is of utmost significance in myocardial ischemia-reperfusion (I/R) injury. Irisin, a myokine, has drawn extensive attention in research regarding the protection against cardiovascular diseases.</p><p><strong>Methods: </strong>This study utilized in vitro Hypoxia/Reoxygenation (H/R) models in H9c2 cardiomyocytes to simulate I/R injury. Cells were pretreated with irisin (20 ng/mL) prior to reoxygenation. UCP2 knockdown was achieved via siRNA/shRNA transfection. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry (Annexin V-FITC/PI staining), respectively. Intracellular calcium dynamics were monitored by Fluo-3/AM confocal imaging, while ROS levels were quantified via DCFH-DA flow cytometry. Key oxidative stress markers (LDH, MDA, GSH-Px, and CAT) and protein expression (ASC, NLRP3, SIRT1, UCP2, and SOD2) were evaluated using commercial kits and Western blotting. Protein interactions were analyzed by coimmunoprecipitation, and ubiquitination levels were measured under proteasomal/lysosomal inhibition (MG132/Leupeptin).</p><p><strong>Results: </strong>Irisin attenuated H/R injury in cardiomyocytes by suppressing apoptosis, calcium/ROS overload, and NLRP3 activation through a UCP2-dependent pathway. UCP2 knockdown significantly attenuated irisin's protection and reduced SOD2 protein stability. Mechanistically, UCP2 bound SOD2 and inhibited its ubiquitin-proteasomal degradation.</p><p><strong>Discussion: </strong>This study reveals a novel mechanism where irisin enhances mitochondrial redox homeostasis by promoting UCP2's function, which stabilizes SOD2 against ubiquitin-proteasomal degradation. This UCP2-SOD2 axis attenuates oxidative stress and inhibits NLRP3 inflammasome activation during cardiac injury, offering a promising dual-targeted therapeutic strategy for I/R injury.</p><p><strong>Conclusion: </strong>Irisin protects cardiomyocytes against H/R injury primarily via a novel UCP2-SOD2 axis.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MOTS-c Protects Against Acetaminophen-induced Liver Injury through the MAPK Signaling Pathway.","authors":"Nan Li, Yimin Xu, Qixin Chen, Jinhong Jiang, Wei Wei Li","doi":"10.2174/0109298665430028251230103831","DOIUrl":"https://doi.org/10.2174/0109298665430028251230103831","url":null,"abstract":"<p><strong>Objective: </strong>Acetaminophen (APAP)-induced liver injury (AILI) is a leading cause of acute liver failure worldwide, but effective therapeutic strategies are still lacking. MOTS-c, a mitochondrial-derived peptide, has demonstrated hepatoprotective properties in models of nonalcoholic steatohepatitis (NASH) and hepatitis B virus (HBV) infection. This study aims to explore the role and underlying mechanisms of MOTS-c in AILI.</p><p><strong>Methods: </strong>An AILI model was established in male C57BL/6 mice via intraperitoneal (i.p.) injection of APAP (300 mg/kg). The therapeutic potential of MOTS-c and its mechanisms were assessed using behavioral tests, qPCR, western blotting, ELISA, immunohistochemistry, immunofluorescence, and TUNEL staining.</p><p><strong>Results: </strong>MOTS-c levels in both plasma and liver tissues were significantly reduced in APAPinduced AILI mice compared with controls. Administration of MOTS-c via i.p. injection markedly attenuated APAP-induced increases in AST and ALT levels, histopathological liver damage, and other liver injury markers. MOTS-c treatment suppressed the release of pro-inflammatory factors (TNF-α, IL-1β, IL-6, and COX-2) and macrophage infiltration induced by APAP. Furthermore, MOTS-c treatment significantly restored GSH content, diminished reactive oxygen species (ROS) production, and oxidative stress. TUNEL staining confirmed that increased apoptosis in APAPtreated livers was significantly attenuated by MOTS-c, which are key contributors to hepatocyte death and liver injury. Mechanistic studies revealed that MOTS-c inhibited APAP-induced phosphorylation of MAPK pathway components, including ERK, JNK, and p38. The protective effects of MOTS-c on serum ALT and AST levels were abolished by co-treatment with inhibitors of ERK, JNK, and p38.</p><p><strong>Discussion: </strong>This study reveals that the mitochondrial peptide MOTS-c can alleviate drug-induced liver injury by suppressing oxidative stress and inflammation via the MAPK pathway. This positions MOTS-c as a promising therapeutic candidate for treating APAP-induced liver injury.</p><p><strong>Conclusion: </strong>This study demonstrates that administering MOTS-c effectively protects against APAP-induced liver injury in mice. The protective mechanism involves suppressing the damaging MAPK signaling pathway (ERK, JNK, p38), which in turn reduces oxidative stress, inflammation, and cell death.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-Wide Acetylome Profiling Suggests Extensive Aspirin-Driven Remodeling of Networks Relevant to THP-1 Macrophage Differentiation.","authors":"Zi-Hui Ma, Yuan-Qing Pan, Pir Tariq Shah, Li Xing","doi":"10.2174/0109298665444488260123052552","DOIUrl":"https://doi.org/10.2174/0109298665444488260123052552","url":null,"abstract":"<p><strong>Introduction: </strong>Acetylsalicylic Acid (aspirin or ASA) is known to exhibit immunomodulatory effects not only through Cyclooxygenase (COX) inhibition but also through direct protein acetylation. However, its impact on innate immune cell differentiation remains unclear.</p><p><strong>Materials and methods: </strong>To fill this gap, the study used quantitative acetyl-proteomics to track changes in the lysine acetylome during THP-1 monocyte differentiation into macrophages following ASA preconditioning.</p><p><strong>Results: </strong>Our results showed that preconditioning of THP-1 macrophages with 300 μg/ml ASA for 3 hours before differentiation induced persistent acetylation changes. We identified 5,199 differentially acetylated sites across 2,678 proteins, with 2,595 sites upregulated and 2,604 downregulated. The sequence analysis revealed a strong preference of ASA for acidic residues like E_K motifs and hydrophobic regions. The subcellular localization analysis showed notable enrichment in the nucleus (1,166 proteins), cytoplasm (850 proteins), and mitochondria (405 proteins), and frequently contained functional domains like PWWP, SET, RhoGEF, and RNA recognition motifs.</p><p><strong>Discussion: </strong>The Gene Ontology analysis linked these proteins to cellular metabolism, regulation, and stimulus response, while our KEGG analysis connected them to neurodegeneration, infection, and metabolic pathways. Furthermore, the protein-protein interaction networks further showed coordinated changes in ribosomal, signaling, and chromatin complexes.</p><p><strong>Conclusion: </strong>The findings show that ASA preconditioning leaves a lasting acetylome signature during macrophage differentiation reprogramming regulatory networks relevant to macrophage differentiation and functional networks via motif-directed acetylation. The results provide a plausible COX-independent model in which structural motif-targeted acetylation may underlie ASA's immunomodulatory role.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Plant-Derived Proteins and Peptides in Leukemia Treatment.","authors":"Zahra Moghaddasi, Azam Bolhassani, Elnaz Agi","doi":"10.2174/0109298665395842250814085828","DOIUrl":"https://doi.org/10.2174/0109298665395842250814085828","url":null,"abstract":"<p><p>Leukemia is one of the most prevalent malignancies worldwide that causes the unusual evolution of hematopoietic stem cells. The type of leukemia determines the optimal treatment plan and the patient's survival. However, finding safer and more effective medications and developing novel therapeutic strategies are still the most challenging research topics. Nowadays, over half of the medications used to treat cancer are derived from natural ingredients. Medicinal plants are a reliable natural source of anti-leukemic medications. Plant-derived biologically active compounds, including secondary metabolites, have long been considered extremely valuable for treating various human illnesses. However, the limitations of secondary metabolites have led scientists to seek alternative biologically active compounds. Plant-derived proteins and peptides have recently been explored as potential treatments for various human ailments, showing anti-microbial, anti-oxidant, anti-HIV, anti-cancer, ribosome-inactivating, and neuromodulatory properties. Until now, no review article has documented the biologically active proteins and peptides against leukemia. This review article explores the therapeutic properties of plant-derived proteins and peptides against leukemia.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Activity of a Defensin-Rich Fraction from Capsicum Chinense Fruits: Insights for Biotechnological Applications against Fungal Infections.","authors":"Mariana C L Aguieiras, Érica O Mello, Larissa M Resende, Gabriel B Taveira, Thaynã A M Souza, Milena B Cherene, Arielle P B F Oliveira, Celso S Nagano, Renata P Chaves, Andre O Carvalho, Rosana Rodrigues, Fernanda Trindade, Maura Da Cunha, Valdirene M Gomes","doi":"10.2174/0109298665377738250626233111","DOIUrl":"https://doi.org/10.2174/0109298665377738250626233111","url":null,"abstract":"<p><strong>Background: </strong>The increasing resistance of fungal pathogens to conventional antifungal treatments has led to a global rise in fungal infections, affecting human health (Candida spp.) and agricultural productivity (Colletotrichum and Fusarium spp.). Antimicrobial peptides (AMPs), such as defensins, have gained attention for their potential in controlling these infections due to their broad-spectrum activity.</p><p><strong>Objectives: </strong>The aim of this study was to partially purify and characterize the antifungal activity of a defensin-enriched fraction (F3) from Capsicum chinense fruits. Specifically, we sought to evaluate its efficacy against pathogenic fungi and yeasts, and to assess the relative abundance of defensins in the fraction.</p><p><strong>Methods: </strong>The F3 fraction was obtained using ion exchange and molecular exclusion chromatography. Reverse-phase chromatography (HPLC) was then employed for further purification. The antifungal activity of F3 was tested against Colletotrichum, Fusarium, and Candida species. Mass spectrometry was used to identify and characterize the defensin (CcDef3) within the fraction. The presence of the defensin relative to other components was inferred from electrophoretic profiles and peptide analysis.</p><p><strong>Results: </strong>The F3 fraction exhibited significant antifungal activity, with growth inhibition of Colletotrichum lindemuthianum of 51% and 60.9% at concentrations of 100 and 200 μg mL-1, respectively. The fraction also inhibited the growth of several Candida species, notably C. nivariensis (93.8%) and C. bracarensis (79.6%) at 100 μg mL-1. Cell viability analysis indicated a fungistatic effect. Fluorescence microscopy assays showed that F3 induced membrane permeabilization in C. parapsilosis and C. lindemuthianum, and increased ROS production in C. pelliculosa and F. solani. The defensin-rich H8 fraction, containing a 6.5 kDa protein (CcDef3), was identified as a major component via mass spectrometry.</p><p><strong>Conclusion: </strong>These results suggest that the F3 fraction, particularly the defensin CcDef3, has potential as an antifungal agent for biotechnological and therapeutic applications. However, further studies are needed to quantify the contribution of CcDef3 relative to other components in the fraction and to fully isolate the defensin for in-depth analysis.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Plant Peptidases for the Production of Therapeutic Peptides.","authors":"Cleverson Diniz Teixeira de Freitas, Jefferson Soares de Oliveira","doi":"10.2174/0109298665373399250319082357","DOIUrl":"https://doi.org/10.2174/0109298665373399250319082357","url":null,"abstract":"<p><p>Peptidases play crucial roles in numerous physiological processes within living organisms. Therefore, they have been employed in various pharmaceutical applications. Plant peptidases have attracted considerable attention in various areas due to their specificity, stability across a diverse range of pH and temperatures, and safety profile. Here, we have focused on the use of plant peptidases, mostly papain and bromelain, to produce biologically active peptides, which confer various health advantages, including antioxidant, antimicrobial, antihypertensive, analgesic, antidiabetic, and anti-inflammatory effects. We have also discussed the importance of the action mechanism of peptidases for generating bioactive peptides with specific sequences and functions, the ecological and sustainability benefits of plant-derived peptidases compared to animal alternatives, digestive stability and bioavailability of peptides, as well as some obstacles to the commercialization of bioactive peptides and key challenges in peptidase-based industrial applications. Finally, we have examined enzyme immobilization as a viable method to enhance the production of bioactive peptides, offering numerous advantages in both research and industry contexts.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived Cyclotides in Immunomodulation and their Therapeutic Potential.","authors":"Reema Mishra, Preeti Agarwal, Anshita Sharma, Meenal Mittal, Pooja Gulati, Aparajita Mohanty","doi":"10.2174/0109298665364479250214101422","DOIUrl":"https://doi.org/10.2174/0109298665364479250214101422","url":null,"abstract":"<p><p>The incidences of immune-related disorders have drastically increased in recent years across the world population. Treatment and management of these diseases, especially autoimmune disorders, are complex and challenging. Available synthetic drugs are not completely effective and also pose serious side effects for the patients. Cyclotides are a class of plant-derived cyclic peptides (28-37 amino acids) with three conserved disulfide linkages establishing a cyclic cystine knot (CCK) motif that makes them very stable biomolecules. Their inherent stability, bioavailability and membrane-penetrating capabilities render them attractive potential pharmacological agents. Studies have demonstrated that cyclotides can either enhance or suppress immune responses, making them versatile candidates for treating various immune-related disorders. Of more than 1000 cyclotides discovered to date, only up to 15 native cyclotides (e.g. kalata B1, pase and caripe cyclotides) have been screened to demonstrate their immunomodulatory activity. Of special significance is the chemically synthesised lysine mutant of kalata B1 viz. [T20K], where preclinical studies have shown promise in the treatment of the autoimmune disorder, multiple sclerosis. In vivo studies in mice models have demonstrated that daily administration of 1mg/day of [T20K] led to a significant decrease in the level of cytokine secretion, lesser demyelination (<1%) and very low inflammatory index (<0.5), in the immunized mice. Moreover, when compared with other immunosuppressive drugs (azathioprine, prednisolone, and cyclosporine A) there was a notable drop in mortality and morbidity in mice administered with [T20K]. The cyclotides, kalata B1 and MCoTI-I have also been used as scaffolds to graft bioactive peptides with immunomodulatory activity. Subsequent in vitro and in vivo studies of these grafted cyclotides have demonstrated their therapeutic ability. Keeping in view the therapeutic potential of cyclotides as immunomodulatory peptides, the present review discusses its current research scenario and implications for the future in tackling immune-related disorders.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of HIF2α Enhances the Angiogenesis-Promoting Effect of hUC-MSC-Derived Extracellular Vesicles by Stimulating miR-146a.","authors":"Yihui Chen, Shichai Hong, Zhefeng Wang, Xiang Hong, Gang Chen, Yulong Huang, Yue Lin, Xinsheng Xie, Chenwei Lin, Weifeng Lu","doi":"10.2174/0109298665347753241028072130","DOIUrl":"10.2174/0109298665347753241028072130","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore whether excessive HIF2α can amplify the impact of human Umbilical Cord Mesenchymal Stem Cell-derived Extracellular Vesicles (hUC-MSC- EVs) on endothelial cells.</p><p><strong>Methods: </strong>In this study, we created HIF2α-overexpressing hUC-MSC-EVs and compared their pro-angiogenic effects with control EVs on Human Umbilical Vein Endothelial Cells (HUVECs). MTT assay and Edu staining were used to detect the viability and proliferation ability of HUVECs, and Transwell and Tube Formation Assays were used to detect cell migration and tube formation ability. qPCR assay was used to detect the expression of cellular angiogenic markers. Subsequently, miRNAs that might be regulated by HIF2α were predicted by bioinformatics analysis, and qPCR was used to detect the relative expression of miRNAs in HUVECs treated with hUC-MSC- EV, which over-expresses HIF2α. Subsequently, miR-146a inhibitors were used to investigate the role of miR-146a in mediating the pro-angiogenic effect of HIF2α on HUVECs by detecting cell viability, proliferation, migration, tube-forming ability, and expression of angiogenic markers. Finally, AKT/ERK phosphorylation and Spred1 expression were detected using Western blotting.</p><p><strong>Results: </strong>Our findings have indicated that overexpression of HIF2α significantly enhances the ability of hUC-MSC-EVs to stimulate proliferation, migration, and tube formation in HUVECs, as demonstrated by MTT/Edu staining, Transwell assay, and tube formation assay results, respectively. Mechanistically, excessive HIF2α has been found to induce the expression of miR-146a in HUVECs and the overexpression of a miR-146a inhibitor to negate the influence of excessive HIF2α on hUC-MSC-EV-induced activity in HUVECs.</p><p><strong>Conclusion: </strong>The overexpression of HIF2α is an effective strategy for enhancing the pro-angiogenic function of hUC-MSC-EVs.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"62-74"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}