Research

Thymosin B4 Reduces Inflammation by Upregulating MicroRNA-146a and Promotes Myelin

“Tissue inflammation results from neurological injury, and regulation of the inflammatory response is vital for neurological recovery. The innate immune response system, which includes the Toll-like receptor (TLR) proinflammatory signaling pathway, regulates tissue injury… TB4-mediated oligodendrogenesis results from [up-regulating] miR-146a [causing the] suppression [of] the TLR proinflammatory pathway and modulation of the p38 MAPK pathway.” (8)“By targeting IRAK1 and TRAF6, miR-146 inhibits NF-κB activation. We therefore hypothesized that TB4 regulates the TLR proinflammatory signaling pathway by specifically regulating miR-146a to promote differentiation of OPCs [oligodendrocyte progenitor cells] to mature myelin basic protein (MBP)-expressing OLs [oligodendrocytes]… transfection with anti-miR-146a inhibitor nucleotides significantly inhibited the expression of MBP and phosphorylation of p38 MAPK.” (8)

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)

TB-500 also known as Thymosin Beta 4 is a naturally occurring peptide. It is found in high concentrations in blood platelets, wound fluid and other tissues in the body. TB-500 is not a growth factor; rather, it is a major actin regulating peptide. TB-500 (Thymosin Beta 4) has been found to play an important role in protection, regeneration and remodeling of injured or damaged tissues. The gene for TB-500 (Thymosin Beta 4) has also been found to be one of the first to be upregulated after a wound occurs.