LncRNA HOTAIR promotes myocardial fibrosis in atrial fibrillation through binding with PTBP1 to increase the stability of Wnt5a.

Abstract

BACKGROUND:

Atrial fibrillation (AF) is one of the most common arrhythmia in clinical practice, and atrial fibrosis is the important mediator in AF. LncRNA HOTAIR was reported to be up-regulated in AF, while the underlying mechanism of HOTAIR in AF remains unclear.

METHODS:

In vitro and in vivo AF model was established. qRT-PCR and Western blotting were used to assess the mRNA expression (HOTAIR, Wnt5a and PTBP1) and protein levels (Wnt5a, collagen I/III, α-SMA, CTGF, p-ERK, ERK, p-JNK, and JNK), respectively. MTT, CCK8, transwell assay was used to test cell viability, proliferation and migration, respectively. RIP assay assessed the correlation among HOTAIR, PTBP1 and Wnt5a. The level of α-SMA was detected by immunofluorescence. HE and Masson staining detected the histological changes and fibrosis in mouse heart tissues.

RESULTS:

Ang II significantly increased the viability of atrial fibroblasts. The levels of HOTAIR and Wnt5a in fibroblasts were up-regulated by Ang II. HOTAIR silencing or Wnt5a significantly inhibited Ang II-induced proliferation, migration and fibrosis in fibroblasts. HOTAIR silencing repressed Wnt5a-mediated ERK and JNK signaling pathway, and Wnt5a partially abolished the effect of HOTAIR silencing on cell proliferation, migration and fibrosis. Meanwhile, HOTAIR could increase the mRNA stability of Wnt5a via recruiting PTBP1. Furthermore, HOTAIR knockdown notably inhibited the fibrosis in heart tissues of AF mice via regulation of Wnt signaling.

CONCLUSION:

HOTAIR could promote atrial fibrosis in AF through binding with PTBP1 to increase Wnt5a stability. Our study might shed new insights on exploring new strategies against AF.

• Authors: Wei Tan, Kun Wang, Xue Yang, Kun Wang, Ning Wang, Ting-Bo Jiang
• Journal: International journal of cardiology (Int J Cardiol) Vol. 369 Pg. 21-28 (12 15 2022) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 35787431 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Collagen Type I
• HOTAIR long non-coding RNA, mouse
• Heterogeneous-Nuclear Ribonucleoproteins
• MicroRNAs
• Ptbp1 protein, mouse
• RNA, Long Noncoding
• RNA, Messenger
• Polypyrimidine Tract-Binding Protein

Topics

• Animals
• Atrial Fibrillation
• Cardiomyopathies (metabolism)
• Collagen Type I
• Fibrosis
• Heterogeneous-Nuclear Ribonucleoproteins
• Mice
• MicroRNAs (genetics)
• Polypyrimidine Tract-Binding Protein (genetics)
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Messenger (genetics)