Abstract
The mammalian heart is capable of achieving perfect regeneration following cardiac injury through sustained cardiomyocyte proliferation during the early period after birth. However, this regenerative capacity is lost by postnatal day 7 and throughout adulthood. CUGBP1 is critical for normal cardiac development but its role in heart regeneration remains unclear. Cardiac CUGBP1 levels are high in the early postnatal period and soon downregulate to adult levels within 1 week following birth in mice. The simultaneously diminished regenerative capacity and CUGBP1 levels by postnatal day lead us to hypothesize that CUGBP1 may be beneficial in heart regeneration. In this study, the function of CUGBP1 in heart regeneration was tested by a heart apex resection mouse model. We demonstrate that cardiac inactivation of CUGBP1 impairs neonatal heart regeneration at P1, in turn, replenishment of CUGBP1 levels prolong regenerative potential at P8 and P14. Furthermore, our results imply that the Wnt/β-catenin signaling and GATA4 involve in the CUGBP1 modulated neonatal heart regeneration. Altogether, our findings support CUGBP1 as a key factor promoting post-injury heart regeneration and provide a potential therapeutic method for heart disease.
Highlights
The adult mammalian heart has limited capacity for regeneration or repair, which is insufficient to restore contractile function following injury and disease [1, 2]
CUG triplet repeat RNA binding protein 1 (CUGBP1) abundance is upregulated upon apical resection In order to investigate the expression pattern of CUGBP1 in the process of heart regeneration in newborn mice, apical resection was performed on 1-day-old (P1) and 8-day-old (P8) mice
These results suggest that CUGBP1 may play a role in regeneration of heart injury in newborn mice
Summary
The adult mammalian heart has limited capacity for regeneration or repair, which is insufficient to restore contractile function following injury and disease [1, 2]. Zebrafish shows a high capacity for heart regeneration throughout life and is capable of full recovery from significant injury [3]. The neonatal mouse heart retains significant cardiac regenerative potential after apical resection [4]. The regenerative response is lost within 7 days after birth and remains absent in adult hearts, which is replaced by a fibrotic response and pathological hypertrophy [4]. It is crucial to understand the molecular mechanisms that regulate cardiac regenerative capacity in mammals and extending the time window of mammalian heart regeneration, which represents an important issue for cardiovascular regenerative medicine
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