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Updated: Oct 23, 2025
Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Downregulation of Hotair or LSD1 Impaired Heart Regeneration in the Neonatal Mouse
Qiaoman Fei1,2, Manman Qiu1, Guanwei Fan3
1Department of Physiology, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Insights
HOX transcript antisense RNA (Hotair) and lysine-specific demethylase 1 (LSD1) are crucial for neonatal mouse heart regeneration. Inhibiting their expression halts myocardial regeneration and cardiomyocyte proliferation.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Developmental Biology
Background:
- Lysine-specific demethylase 1 (LSD1) regulates cell cycle progression via demethylation.
- The HOX transcript antisense RNA (Hotair) 3' domain, with the LSD1/CoREST/REST complex, targets LSD1 to specific genes.
- The role of Hotair and LSD1 in neonatal mouse myocardial regeneration remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of Hotair and LSD1 in the myocardial regeneration of neonatal mice.
- To determine the expression patterns of Hotair and LSD1 during the critical window of neonatal heart regeneration.
Main Methods:
- Quantitative analysis of Hotair and Lsd1 expression in neonatal mouse hearts.
- RNA interference (RNAi) to knockdown Lsd1 and Hotair expression.
- Assessment of myocardial regeneration and cardiomyocyte proliferation following gene knockdown.
Main Results:
- Myocardial tissue exhibits high expression of Hotair and Lsd1 within the first week after birth, coinciding with the regenerative period.
- Knockdown of Lsd1 or Hotair significantly inhibited myocardial regeneration.
- Reduced cardiomyocyte proliferation was observed upon Lsd1 or Hotair knockdown.
Conclusions:
- Hotair and LSD1 expression are temporally correlated with the regenerative capacity of neonatal mouse hearts.
- Hotair-mediated demethylation by LSD1 is a key mechanism promoting myocardial regeneration in neonatal mice.
- Targeting the Hotair-LSD1 pathway may offer therapeutic potential for cardiac repair.
Abstract:
Previous studies have shown that lysine-specific demethylase 1 (LSD1) could regulate cell cycle progression through demethylation. The 3'domain of HOX transcript antisense RNA (Hotair) combined with the LSD1/CoREST/REST complex helps LSD1 target the corresponding gene. However, its role in mice's myocardial regeneration is still unclear. The heart from neonatal mice shows strong myocardial regeneration ability, but this ability disappears 7 days after birth. Our study shows that the myocardial tissue highly expresses Hotair and Lsd1 within 1 week after birth, consistent with the myocardial regeneration time window. Knockdown Lsd1 or Hotair expression by RNA interference could inhibit myocardial regeneration and cardiomyocyte proliferation. Our results suggest that Hotair-mediated demethylation of LSD1 may play an important role in myocardial regeneration in neonatal mice.
