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11 August 2020 : Laboratory Research  

Nkx2–5 Regulates the Proliferation and Migration of H9c2 Cells

Hongshu Wang1BCDEF, Yong Liu2BC, Shen Han1B, Yunfeng Zi1B, Yayong Zhang1B, Ruize Kong3B, Zu Liu1B, Zhibin Cai1B, Chongbin Zhong4B, Wei Liu5B, Lifeng Li4B, Lihong Jiang3AG*

DOI: 10.12659/MSM.925388

Med Sci Monit 2020; 26:e925388

Abstract

BACKGROUND: The protein NKX2–5 affects mammalian heart development. In mice, the disruption of Nkx2–5 has been associated with arrhythmias, abnormal myocardial contraction, abnormal cardiac morphogenesis, and death. However, the details of the mechanisms are unclear. This study was designed to investigate them.

MATERIAL AND METHODS: Rat cardiomyocytes from the H9c2 cell line were used in our study. First, we knocked down Nkx2–5 in the H9c2 cells and then validated consequent changes in cell proliferation and migration. We then used RNA sequencing to determine the changes in transcripts. Finally, we validated these results by quantitative reverse transcription-polymerase chain reaction.

RESULTS: We confirmed that Nkx2–5 regulates the proliferation and migration of H9c2 cells. In our experiments, Nkx2–5 regulated the expression of genes related to proliferation, migration, heart development, and disease. Based on bioinformatics analysis, knockdown of Nkx2–5 caused differential expression of genes involved in cardiac development, calcium ion-related biological activity, the transforming growth factor (TGF)-β signaling pathway, pathways related to heart diseases, the MAPK signaling pathway, and other biological processes and signaling pathways.

CONCLUSIONS: Nkx2–5 may regulate proliferation and migration of the H9c2 cells through the genes Tgfb-2, Bmp10, Id2, Wt1, Hey1, and Cacna1g; rno-miR-1-3p; the TGF‑β signaling pathway; the MAPK signaling pathway; as well as other genes and pathways.

Keywords: Heart Defects, Congenital, MAP Kinase Signaling System, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750