Integrated whole transcriptome analysis for the crucial regulators and functional pathways related to cardiac fibrosis in rats

Shuai Miao; Lijun Wang; Siyu Guan; Tianshu Gu; Hualing Wang; Wenfeng Shangguan; Weiding Wang; Yu Liu; Xue Liang; Shuai Miao; Lijun Wang; Siyu Guan; Tianshu Gu; Hualing Wang; Wenfeng Shangguan; Weiding Wang; Yu Liu; Xue Liang

doi:10.3934/mbe.2023250

Mathematical Biosciences and Engineering

2023, Volume 20, Issue 3: 5413-5429. doi: 10.3934/mbe.2023250

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Research article

Integrated whole transcriptome analysis for the crucial regulators and functional pathways related to cardiac fibrosis in rats

1.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China
2.
Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China
3.
Taikang Ningbo Hospital, Ningbo 315100, Zhejiang, China

† These authors contributed equally.
Academic Editor: Ulf Schmitz

Received: 30 October 2022 Revised: 17 December 2022 Accepted: 25 December 2022 Published: 12 January 2023

Background
Cardiac fibrosis has gradually gained significance in the field of cardiovascular disease; however, its specific pathogenesis remains unclear. This study aims to establish the regulatory networks based on whole-transcriptome RNA sequencing analyses and reveal the underlying mechanisms of cardiac fibrosis.

Methods
An experimental model of myocardial fibrosis was induced using the chronic intermittent hypoxia (CIH) method. Expression profiles of long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) were acquired from right atrial tissue samples of rats. Differentially expressed RNAs (DERs) were identified, and functional enrichment analysis was performed. Moreover, a protein-protein interaction (PPI) network and competitive endogenous RNA (ceRNA) regulatory network that are related to cardiac fibrosis were constructed, and the relevant regulatory factors and functional pathways were identified. Finally, the crucial regulators were validated using qRT-PCR.

Results
DERs, including 268 lncRNAs, 20 miRNAs, and 436 mRNAs, were screened. Further, 18 relevant biological processes, such as "chromosome segregation, " and 6 KEGG signaling pathways, such as "cell cycle, " were significantly enriched. The regulatory relationship of miRNA–mRNA–KEGG pathways showed eight overlapping disease pathways, including "pathways in cancer." In addition, crucial regulatory factors, such as Arnt2, WNT2B, GNG7, LOC100909750, Cyp1a1, E2F1, BIRC5, and LPAR4, were identified and verified to be closely related to cardiac fibrosis.

Conclusion
This study identified the crucial regulators and related functional pathways in cardiac fibrosis by integrating the whole transcriptome analysis in rats, which might provide novel insights into the pathogenesis of cardiac fibrosis.
- cardiac fibrosis,
- whole-transcriptome RNA sequencing,
- functional pathways,
- competing endogenous RNA,
- regulatory network
Citation: Shuai Miao, Lijun Wang, Siyu Guan, Tianshu Gu, Hualing Wang, Wenfeng Shangguan, Weiding Wang, Yu Liu, Xue Liang. Integrated whole transcriptome analysis for the crucial regulators and functional pathways related to cardiac fibrosis in rats[J]. Mathematical Biosciences and Engineering, 2023, 20(3): 5413-5429. doi: 10.3934/mbe.2023250

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Abstract

Background

Cardiac fibrosis has gradually gained significance in the field of cardiovascular disease; however, its specific pathogenesis remains unclear. This study aims to establish the regulatory networks based on whole-transcriptome RNA sequencing analyses and reveal the underlying mechanisms of cardiac fibrosis.

Methods

An experimental model of myocardial fibrosis was induced using the chronic intermittent hypoxia (CIH) method. Expression profiles of long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) were acquired from right atrial tissue samples of rats. Differentially expressed RNAs (DERs) were identified, and functional enrichment analysis was performed. Moreover, a protein-protein interaction (PPI) network and competitive endogenous RNA (ceRNA) regulatory network that are related to cardiac fibrosis were constructed, and the relevant regulatory factors and functional pathways were identified. Finally, the crucial regulators were validated using qRT-PCR.

Results

DERs, including 268 lncRNAs, 20 miRNAs, and 436 mRNAs, were screened. Further, 18 relevant biological processes, such as "chromosome segregation, " and 6 KEGG signaling pathways, such as "cell cycle, " were significantly enriched. The regulatory relationship of miRNA–mRNA–KEGG pathways showed eight overlapping disease pathways, including "pathways in cancer." In addition, crucial regulatory factors, such as Arnt2, WNT2B, GNG7, LOC100909750, Cyp1a1, E2F1, BIRC5, and LPAR4, were identified and verified to be closely related to cardiac fibrosis.

Conclusion

This study identified the crucial regulators and related functional pathways in cardiac fibrosis by integrating the whole transcriptome analysis in rats, which might provide novel insights into the pathogenesis of cardiac fibrosis.

References

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