{"title":"年轻和年长捐献者的循环外泌体对脐带血造血干细胞中缺氧诱导因子 1 Alpha 基因表达和 P21 蛋白的影响","authors":"Zahra Rasti, Reza Afrisham, Elahe Bahrami Vahdat, Zahra Kashanikhatib, Seyed Hadi Mousavi, Shaban Alizadeh","doi":"10.14740/jh1291","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Exosomes are a group of extracellular vesicles that are influential in intercellular signaling and can affect aging. Hypoxia-inducible factor 1α (HIF-1α) is the principal mediator in response to hypoxia and can regulate aging. Moreover, P21 is a part of the downstream signaling pathway of hypoxia and is elevated during aging. Therefore, this research was conducted to investigate the effect of plasma exosomes of younger and older individuals on the expression of <i>HIF-1α</i> gene and P21 protein in hematopoietic stem cells (HSCs).</p><p><strong>Methods: </strong>Plasma exosomes were derived from older and younger men and were characterized. Then, HSCs were isolated from cord blood samples and treated with exosomes of older and younger men. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to evaluate cell viability. Next, the expression of <i>HIF-1α</i> gene and P21 protein were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively.</p><p><strong>Results: </strong><i>HIF-1α</i> gene expression was considerably increased in HSCs treated with 10 µg/mL of exosomes isolated from younger men (Y10-Exo) compared to the untreated group (P = 0.002). Moreover, <i>HIF-1α</i> gene expression was remarkably decreased in HSCs treated with 10 µg/mL of exosomes obtained from older men (O10-Exo) in comparison with the untreated group (P < 0.001). Additionally, the expression of P21 protein was significantly increased in HSCs treated with 5 µg/mL of exosomes derived from older individuals (O5-Exo) and O10-Exo compared to the untreated group (P = 0.000 and P = 0.002, respectively).</p><p><strong>Conclusions: </strong>Our findings showed that exosomes isolated from younger participants cause elevation in HIF-1α and may lead to delayed aging in HSCs. In addition, exosomes isolated from older participants can probably lead to aging through the reduction in HIF-1α and elevation in P21.</p>","PeriodicalId":15964,"journal":{"name":"Journal of hematology","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526583/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Influence of Circulating Exosomes Derived From Younger and Older Donors on Hypoxia-Inducible Factor 1 Alpha Gene Expression and P21 Protein in Cord Blood Hematopoietic Stem Cells.\",\"authors\":\"Zahra Rasti, Reza Afrisham, Elahe Bahrami Vahdat, Zahra Kashanikhatib, Seyed Hadi Mousavi, Shaban Alizadeh\",\"doi\":\"10.14740/jh1291\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Exosomes are a group of extracellular vesicles that are influential in intercellular signaling and can affect aging. Hypoxia-inducible factor 1α (HIF-1α) is the principal mediator in response to hypoxia and can regulate aging. Moreover, P21 is a part of the downstream signaling pathway of hypoxia and is elevated during aging. Therefore, this research was conducted to investigate the effect of plasma exosomes of younger and older individuals on the expression of <i>HIF-1α</i> gene and P21 protein in hematopoietic stem cells (HSCs).</p><p><strong>Methods: </strong>Plasma exosomes were derived from older and younger men and were characterized. Then, HSCs were isolated from cord blood samples and treated with exosomes of older and younger men. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to evaluate cell viability. Next, the expression of <i>HIF-1α</i> gene and P21 protein were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively.</p><p><strong>Results: </strong><i>HIF-1α</i> gene expression was considerably increased in HSCs treated with 10 µg/mL of exosomes isolated from younger men (Y10-Exo) compared to the untreated group (P = 0.002). Moreover, <i>HIF-1α</i> gene expression was remarkably decreased in HSCs treated with 10 µg/mL of exosomes obtained from older men (O10-Exo) in comparison with the untreated group (P < 0.001). Additionally, the expression of P21 protein was significantly increased in HSCs treated with 5 µg/mL of exosomes derived from older individuals (O5-Exo) and O10-Exo compared to the untreated group (P = 0.000 and P = 0.002, respectively).</p><p><strong>Conclusions: </strong>Our findings showed that exosomes isolated from younger participants cause elevation in HIF-1α and may lead to delayed aging in HSCs. In addition, exosomes isolated from older participants can probably lead to aging through the reduction in HIF-1α and elevation in P21.</p>\",\"PeriodicalId\":15964,\"journal\":{\"name\":\"Journal of hematology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526583/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of hematology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14740/jh1291\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of hematology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14740/jh1291","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/21 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
The Influence of Circulating Exosomes Derived From Younger and Older Donors on Hypoxia-Inducible Factor 1 Alpha Gene Expression and P21 Protein in Cord Blood Hematopoietic Stem Cells.
Background: Exosomes are a group of extracellular vesicles that are influential in intercellular signaling and can affect aging. Hypoxia-inducible factor 1α (HIF-1α) is the principal mediator in response to hypoxia and can regulate aging. Moreover, P21 is a part of the downstream signaling pathway of hypoxia and is elevated during aging. Therefore, this research was conducted to investigate the effect of plasma exosomes of younger and older individuals on the expression of HIF-1α gene and P21 protein in hematopoietic stem cells (HSCs).
Methods: Plasma exosomes were derived from older and younger men and were characterized. Then, HSCs were isolated from cord blood samples and treated with exosomes of older and younger men. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to evaluate cell viability. Next, the expression of HIF-1α gene and P21 protein were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively.
Results: HIF-1α gene expression was considerably increased in HSCs treated with 10 µg/mL of exosomes isolated from younger men (Y10-Exo) compared to the untreated group (P = 0.002). Moreover, HIF-1α gene expression was remarkably decreased in HSCs treated with 10 µg/mL of exosomes obtained from older men (O10-Exo) in comparison with the untreated group (P < 0.001). Additionally, the expression of P21 protein was significantly increased in HSCs treated with 5 µg/mL of exosomes derived from older individuals (O5-Exo) and O10-Exo compared to the untreated group (P = 0.000 and P = 0.002, respectively).
Conclusions: Our findings showed that exosomes isolated from younger participants cause elevation in HIF-1α and may lead to delayed aging in HSCs. In addition, exosomes isolated from older participants can probably lead to aging through the reduction in HIF-1α and elevation in P21.
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