Yixin Chen, Qian Zhao, Tengfei Wu, Feifei Sun, Weineng Fu
{"title":"Knockdown of KLF6 ameliorates myocardial infarction by regulating autophagy via transcriptional regulation of PTTG1.","authors":"Yixin Chen, Qian Zhao, Tengfei Wu, Feifei Sun, Weineng Fu","doi":"10.1152/ajpcell.00191.2024","DOIUrl":null,"url":null,"abstract":"<p><p>Krüppel-like factor 6 (KLF6) knockdown provides protection against kidney ischemia/reperfusion (I/R) injury and ischemic stroke. However, it is unclear whether it plays a role in myocardial infarction (MI) remains unknown. Here, the expression of KLF6 was analyzed using the GEO database and determined in patients with MI. The impact of KLF6 knockdown was further confirmed in <i>in vivo</i> and ><i>in vitro</i> models of MI. The interaction between KLF6 and PTTG1 was also evaluated. According to the GEO database, KLF6 expression was found to be upregulated in mouse hearts after MI compared to sham-operated mice. The upregulation of KLF6 in hearts from mice post-MI and in patients with MI was confirmed. KLF6 knockdown was found to alleviate myocardial injury, diminish infarct size, and suppress apoptosis and autophagy in mice with MI. Additionally, inactivation of the AMPK/mTOR signaling was observed after KLF6 knockdown in mice with MI. In an <i>in vitro</i> model of MI, knockdown of KLF6 increased cell survival and inhibited autophagy through the AMPK/mTOR pathway. Additionally, KLF6 interacted with the promoter of PTTG1 and negatively regulated its expression. Knockdown of PTTG1 abolished the function of KLF6 knockdown <i>in vitro</i>. This study demonstrates the protective effect of KLF6 knockdown against MI, which is attributed to the elevation of PTTG1 expression and inhibition of the AMPK/mTOR pathway. These findings provide a novel insight into MI treatment.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Cell physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1152/ajpcell.00191.2024","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Krüppel-like factor 6 (KLF6) knockdown provides protection against kidney ischemia/reperfusion (I/R) injury and ischemic stroke. However, it is unclear whether it plays a role in myocardial infarction (MI) remains unknown. Here, the expression of KLF6 was analyzed using the GEO database and determined in patients with MI. The impact of KLF6 knockdown was further confirmed in in vivo and >in vitro models of MI. The interaction between KLF6 and PTTG1 was also evaluated. According to the GEO database, KLF6 expression was found to be upregulated in mouse hearts after MI compared to sham-operated mice. The upregulation of KLF6 in hearts from mice post-MI and in patients with MI was confirmed. KLF6 knockdown was found to alleviate myocardial injury, diminish infarct size, and suppress apoptosis and autophagy in mice with MI. Additionally, inactivation of the AMPK/mTOR signaling was observed after KLF6 knockdown in mice with MI. In an in vitro model of MI, knockdown of KLF6 increased cell survival and inhibited autophagy through the AMPK/mTOR pathway. Additionally, KLF6 interacted with the promoter of PTTG1 and negatively regulated its expression. Knockdown of PTTG1 abolished the function of KLF6 knockdown in vitro. This study demonstrates the protective effect of KLF6 knockdown against MI, which is attributed to the elevation of PTTG1 expression and inhibition of the AMPK/mTOR pathway. These findings provide a novel insight into MI treatment.
期刊介绍：
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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