Thymosin β4 and Prothymosin α Promote Cardiac Regeneration Post-Ischaemic Injury in Mice
“The adult mammalian heart is a post-mitotic organ. Even in response to necrotic injuries, where regeneration would be essential to reinstate cardiac structure and function, only a minor percentage of cardiomyocytes undergo cytokinesis… In this study, we aimed to determine the gene expression profile of proliferating adult cardiomyocytes in the mammalian heart after myocardial ischaemia, to identify factors to can promote cardiac regeneration… Here, we demonstrate increased 5-ethynyl-2’deoxyuridine incorporation in cardiomyocytes 3 days post-myocardial infarction in mice… Combinatorial overexpression of the enriched genes within this population in neonatal rat cardiomyocytes and mice at postnatal day 12 (P12) unveiled key genes that promoted increased cardiomyocyte proliferation. Therapeutic delivery of these gene cocktails into the myocardial wall after ischaemic injury demonstrated that a combination of thymosin beta 4 (TMSB4) and prothymosin alpha (PTMA) provide a permissive environment for cardiomyocyte proliferation and thereby attenuated cardiac dysfunction… This study reveals the transcriptional profile of proliferating cardiomyocytes in the ischaemic heart and shows that overexpression of the two identified factors, TMSB4 and PTMA, can promote cardiac regeneration.” (2)
The Role of Thymosin β4 in Cardiomyocyte Proliferation and Cardiac Regeneration
“Thymosin β4 (Tβ4) is a 43-amino acid protein that belongs to the β-thymosin family, which is highly conserved… Tβ4 has been associated with wound healing, inflammation, fibrosis, and tissue regeneration, with recent studies suggesting that Tβ4 can help prevent inflammation and fibrosis in the eye, skin, lung, and liver… Tβ4 is a potent protective factor that can protect against myocyte damage, promote myocyte regeneration, and inhibit heart inflammation… Therefore, we propose that Tβ4 might have an antifibrotic function in the heart.” (3)
