Thymosin β<sub>4</sub>: a multi-functional regenerative peptide. Basic properties and clinical applications

Goldstein, Allan L.; Hannappel, Ewald; Sosne, Gabriel; Kleinman, Hynda K.

doi:10.1517/14712598.2012.634793

Cited by 119 publications

(101 citation statements)

References 91 publications

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“…The tests performed with rats and dogs, which were administered endogenous Tβ4, showed no significant adverse effects of the protein. In the tests already carried out with humans, the results are promising, and provide evidence of the safety and efficacy in the therapeutic effect of Tβ4 use [28].…”

Section: Therapeutic Potential Of Tβ4mentioning

confidence: 86%

“…Major activities which it exhibits are: actin binding, promotion of cell migration, angiogenesis, an anti-inflammatory and anti-apoptotic action, promoting wound healing, inhibition of fibrosis, stem cell recruitment and differentiation., protection from burns, cytotoxic agents and hypoxia [7,24,25,27,28,30,33]. It is worth noting that disturbances in the expression of this protein may have serious clinical consequences, particularly in the context of cancer [6,36,1,23].…”

Section: Discussionmentioning

confidence: 99%

“…To test the safety of a formulation containing Tβ4, a series of experiments was done. On the basis of trials with transgenic mice, it appears that an excess (50 fold) of the protein did not result in adverse side effects in survival, but only had a negative impact on the development of dentition during fetal growth [28]. The tests performed with rats and dogs, which were administered endogenous Tβ4, showed no significant adverse effects of the protein.…”

Section: Therapeutic Potential Of Tβ4mentioning

confidence: 98%

“…The results were positive, the thymosin treated animals exhibited greater survival of myocardial cells and reduced scar formation by 53% at 4 weeks. The migration of progenitor cells from the inner layers of the heart and their differentiation into new coronary vessels was also found [28].…”

Section: Thymosin As a Factor Which Regulates Inhibition Of Scarringmentioning

confidence: 99%

“…As a result, the coronary arteries are less numerous, tissue has abnormal structure and is poorly supplied with blood and nourished [27]. It was also discovered that Tβ4 may mobilize progenitor cells from the circulation, as well as from the epicardium [28]. The discovery of this mechanism may be important in the therapeutic strategies of cardiac diseases, in the regeneration of heart cells in patients after myocardial infarction or long-term ischemic disease.…”

Section: Tβ4 In the Functioning Of The Heartmentioning

confidence: 99%

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Thymosin β as an Actin-binding Protein with a Variety of Functions

Kuzan

2016

Adv Clin Exp Med

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Section: Therapeutic Potential Of Tβ4mentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Therapeutic Potential Of Tβ4mentioning

confidence: 98%

Section: Thymosin As a Factor Which Regulates Inhibition Of Scarringmentioning

confidence: 99%

Section: Tβ4 In the Functioning Of The Heartmentioning

confidence: 99%

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Thymosin β as an Actin-binding Protein with a Variety of Functions

Kuzan

2016

Adv Clin Exp Med

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Detection and quantification of the metabolite Ac‐Tβ_1–14 in in vitro experiments and urine of rats treated with Ac‐Tβ4: A potential biomarker of Ac‐Tβ4 for doping tests

Rahaman

Muresan

Hasan

et al. 2023

Drug Testing and Analysis

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Thymosin β4 (Tβ4) was reported to exert various beneficial bioactivities such as tissue repair, anti‐inflammation, and reduced scar formation, and it is listed on the prohibited substances in sports by the World Anti‐Doping Agency. However, no metabolism studies of Tβ4 were reported yet. Previously, our lab reported in in vitro experiment that a total of 13 metabolites were found by using multiple enzymes, and six metabolites (Ac‐Tβ31–43, Ac‐Tβ17–43, Ac‐Tβ1–11, Ac‐Tβ1–14, Ac‐Tβ1–15, and Ac‐Tβ1–17) were confirmed by comparing with the synthetic standards. This study was aimed at identifying new metabolites of Tβ4 leucine aminopeptidase (LAP), human kidney microsomes (HKM), cultured huvec cells, and rats after administration of Tβ4 protein to develop biomarkers for detecting doping drugs in sports. A method for detecting and quantifying Ac‐Tβ1–14 was developed and validated using Q‐Exactive orbitrap mass spectrometry. The limit of detection (LOD) and limit of quantification (LOQ) of the Ac‐Tβ1–14 were 0.19 and 0.58 ng/mL, respectively, and showed a good linearity (r2 = 0.9998). As a result, among the six metabolites above, Ac‐Tβ1–14, as a common metabolite, was found in LAP, HKM, huvec cells exposed to Tβ4, and the urine of rats intraperitoneally treated with 20‐mg/kg Tβ4. And the metabolite Ac‐Tβ1–14 was quantitatively determined by 48 h in rats, with the highest concentration occurring between 0 and 6 h. Ac‐Tβ1–14 was not detected in non‐treated control groups, including human blank urine. These results suggest that Ac‐Tβ1–14 in urine is a potential biomarker for screening the parent Tβ4 in doping tests.

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Thymosin beta 4 mediates oligodendrocyte differentiation by upregulating p38 MAPK

Santra

Chopp

Zhang

et al. 2012

Glia

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Thymosin beta 4 (Tβ4), a G-actin sequestering peptide, increases oligodendrogenesis and improves functional outcome in models of neurological injury. The molecular mechanisms of Tβ4 mediated oligodendrogenesis are unclear. The p38 mitogen-activated protein kinase (p38MAPK) regulates oligodendrocyte (OL) differentiation and myelin gene expression in other models. Therefore, we investigated p38MAPK signaling pathways. We used primary rat neural progenitor cells (NPCs) and a mouse oligodendrocyte progenitor cell (OPC) line (N20.1 cells) to investigate the molecular mechanisms of Tβ4-enhanced oligodendrogenesis. NPCs were isolated from rat subventricular zone (SVZ) of the lateral ventricles (n=12). Primary NPCs and N20.1 cells were grown in the presence of 0, 25 and 50 ng/ml of Tβ4 (RegeneRx Biopharmaceuticals Inc, Rockville, MD) for 14 days. Quantitative real-time PCR and Western blot data showed significant induction of both expression and phosphorylation of p38MAPK with simultaneous inhibition of phosphorylation of extracellular signal regulated kinase (ERK1), c-Jun N-terminal kinase 1 (JNK1), leading to reduction of phosphorylation of c-Jun, a potent negative regulator of transcription of myelin genes. These effects were reversed with transfection of Tβ4siRNA. Our data indicate that Tβ4 treatment induces OL differentiation by inducing p38MAPK with parallel inactivation of ERK1 and JNK1, thus preventing the accumulation of phosphorylated c-Jun.

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Thymosin β₄: a multi-functional regenerative peptide. Basic properties and clinical applications

Cited by 119 publications

References 91 publications

Thymosin β as an Actin-binding Protein with a Variety of Functions

Thymosin β as an Actin-binding Protein with a Variety of Functions

Detection and quantification of the metabolite Ac‐Tβ_1–14 in in vitro experiments and urine of rats treated with Ac‐Tβ4: A potential biomarker of Ac‐Tβ4 for doping tests

Thymosin beta 4 mediates oligodendrocyte differentiation by upregulating p38 MAPK

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Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications

Cited by 119 publications

References 91 publications

Thymosin β as an Actin-binding Protein with a Variety of Functions

Thymosin β as an Actin-binding Protein with a Variety of Functions

Detection and quantification of the metabolite Ac‐Tβ1–14 in in vitro experiments and urine of rats treated with Ac‐Tβ4: A potential biomarker of Ac‐Tβ4 for doping tests

Thymosin beta 4 mediates oligodendrocyte differentiation by upregulating p38 MAPK

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Product

Resources

About

Thymosin β₄: a multi-functional regenerative peptide. Basic properties and clinical applications

Detection and quantification of the metabolite Ac‐Tβ_1–14 in in vitro experiments and urine of rats treated with Ac‐Tβ4: A potential biomarker of Ac‐Tβ4 for doping tests