MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4
IntroductionThe objective of this study was to determine the NF-kappaB pathway, hub genes, and transcription factors (TFs) in monocytes implicated in the progression of neurovascular-related sepsis-induced cardiomyopathy (SIC) as well as potential miRNAs with regulatory functions.Methods: Sepsis-ind...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.909828/full |
| _version_ | 1828777804463865856 |
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| author | Qiancheng Luo Hanning Ma Enwei Guo Lin Yu Ling Jia Bingyu Zhang Gang Feng Rui Liu |
| author_facet | Qiancheng Luo Hanning Ma Enwei Guo Lin Yu Ling Jia Bingyu Zhang Gang Feng Rui Liu |
| author_sort | Qiancheng Luo |
| collection | DOAJ |
| description | IntroductionThe objective of this study was to determine the NF-kappaB pathway, hub genes, and transcription factors (TFs) in monocytes implicated in the progression of neurovascular-related sepsis-induced cardiomyopathy (SIC) as well as potential miRNAs with regulatory functions.Methods: Sepsis-induced cardiomyopathy—and heart failure (HF)-related differentially expressed genes (DEGs) between SIC and HF groups were identified separately by differential analysis. In addition, DEGs and differentially expressed miRNAs (DEmiRNAs) in monocytes between sepsis and the HC group were identified. Then, common DEGs in SIC, HF, and monocyte groups were identified by intersection analysis. Based on the functional pathways enriched by these DEGs, genes related to the NF-kB-inducing kinase (NIK)/NF-kappaB signaling pathway were selected for further intersection analysis to obtain hub genes. These common DEGs, together with sepsis-related DEmiRNAs, were used to construct a molecular interplay network and to identify core TFs in the network.Results: A total of 153 upregulated genes and 25 downregulated genes were obtained from SIC-, HF-, and monocyte-related DEGs. Functional pathway analysis revealed that the upregulated genes were enriched in NF-κB signaling pathway. A total of eight genes associated with NF-κB signaling pathway were then further identified from the 178 DEGs. In combination with sepsis-related DEmiRNAs, HDAC7/ACTN4 was identified as a key transcriptional regulatory pair in the progression of SIC and in monocyte regulation. hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p can regulate the progression of SIC through the regulation of HDAC7/ACTN4. Finally, gene set enrichment analysis (GSEA) suggested that HDAC7/ACTN4 may be associated with apoptosis in addition to the inflammatory response.Conclusion: hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p are involved in SIC progression by regulating NF-κB signaling signaling pathway-related HDAC7/ACTN4 in monocytes and cardiac tissue cells. These mechanisms may contribute to sepsis-induced neurovascular damage. |
| first_indexed | 2024-12-11T16:29:28Z |
| format | Article |
| id | doaj.art-fa21b96235d047b8bb6ef42797a127e4 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-11T16:29:28Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj.art-fa21b96235d047b8bb6ef42797a127e42022-12-22T00:58:38ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-06-011310.3389/fneur.2022.909828909828MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4Qiancheng Luo0Hanning Ma1Enwei Guo2Lin Yu3Ling Jia4Bingyu Zhang5Gang Feng6Rui Liu7Department of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaDepartment of Emergency Medicine, General Hospital of Ningxia Medical University, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, ChinaIntroductionThe objective of this study was to determine the NF-kappaB pathway, hub genes, and transcription factors (TFs) in monocytes implicated in the progression of neurovascular-related sepsis-induced cardiomyopathy (SIC) as well as potential miRNAs with regulatory functions.Methods: Sepsis-induced cardiomyopathy—and heart failure (HF)-related differentially expressed genes (DEGs) between SIC and HF groups were identified separately by differential analysis. In addition, DEGs and differentially expressed miRNAs (DEmiRNAs) in monocytes between sepsis and the HC group were identified. Then, common DEGs in SIC, HF, and monocyte groups were identified by intersection analysis. Based on the functional pathways enriched by these DEGs, genes related to the NF-kB-inducing kinase (NIK)/NF-kappaB signaling pathway were selected for further intersection analysis to obtain hub genes. These common DEGs, together with sepsis-related DEmiRNAs, were used to construct a molecular interplay network and to identify core TFs in the network.Results: A total of 153 upregulated genes and 25 downregulated genes were obtained from SIC-, HF-, and monocyte-related DEGs. Functional pathway analysis revealed that the upregulated genes were enriched in NF-κB signaling pathway. A total of eight genes associated with NF-κB signaling pathway were then further identified from the 178 DEGs. In combination with sepsis-related DEmiRNAs, HDAC7/ACTN4 was identified as a key transcriptional regulatory pair in the progression of SIC and in monocyte regulation. hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p can regulate the progression of SIC through the regulation of HDAC7/ACTN4. Finally, gene set enrichment analysis (GSEA) suggested that HDAC7/ACTN4 may be associated with apoptosis in addition to the inflammatory response.Conclusion: hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p are involved in SIC progression by regulating NF-κB signaling signaling pathway-related HDAC7/ACTN4 in monocytes and cardiac tissue cells. These mechanisms may contribute to sepsis-induced neurovascular damage.https://www.frontiersin.org/articles/10.3389/fneur.2022.909828/fullneurovascularbiomarkersHDAC7ACTN4microRNANF-kappaB (NF-κB) |
| spellingShingle | Qiancheng Luo Hanning Ma Enwei Guo Lin Yu Ling Jia Bingyu Zhang Gang Feng Rui Liu MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4 Frontiers in Neurology neurovascular biomarkers HDAC7 ACTN4 microRNA NF-kappaB (NF-κB) |
| title | MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4 |
| title_full | MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4 |
| title_fullStr | MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4 |
| title_full_unstemmed | MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4 |
| title_short | MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4 |
| title_sort | micrornas promote the progression of sepsis induced cardiomyopathy and neurovascular dysfunction through upregulation of nf kappab signaling pathway associated hdac7 actn4 |
| topic | neurovascular biomarkers HDAC7 ACTN4 microRNA NF-kappaB (NF-κB) |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.909828/full |
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