Lemei Hu, Chen Jiao, Haiyu Gu, Zhigang Zhu, Ming Liang
{"title":"鉴定和验证白血病抑制因子作为缺血性急性肾损伤的保护因子。","authors":"Lemei Hu, Chen Jiao, Haiyu Gu, Zhigang Zhu, Ming Liang","doi":"10.1016/j.amjms.2024.09.010","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ischemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms.</p><p><strong>Materials and methods: </strong>The RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene.</p><p><strong>Results: </strong>We screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular apoptosis and OS.</p><p><strong>Conclusion: </strong>These findings indicate an important role of the LIF gene in term of regulating apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.</p>","PeriodicalId":94223,"journal":{"name":"The American journal of the medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and validation of leukemia inhibitory factor as a protective factor in ischemic acute kidney injury.\",\"authors\":\"Lemei Hu, Chen Jiao, Haiyu Gu, Zhigang Zhu, Ming Liang\",\"doi\":\"10.1016/j.amjms.2024.09.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ischemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms.</p><p><strong>Materials and methods: </strong>The RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene.</p><p><strong>Results: </strong>We screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular apoptosis and OS.</p><p><strong>Conclusion: </strong>These findings indicate an important role of the LIF gene in term of regulating apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.</p>\",\"PeriodicalId\":94223,\"journal\":{\"name\":\"The American journal of the medical sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The American journal of the medical sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.amjms.2024.09.010\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The American journal of the medical sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.amjms.2024.09.010","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Identification and validation of leukemia inhibitory factor as a protective factor in ischemic acute kidney injury.
Background: Ischemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms.
Materials and methods: The RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene.
Results: We screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular apoptosis and OS.
Conclusion: These findings indicate an important role of the LIF gene in term of regulating apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.