TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair.

Tang S, Fan C, Iroegbu CD, Zhou W, Zhang Z, Wu M, Chen W, Wu X, Peng J, Li Z, Yang J

Frontiers in cell and developmental biology9 Jun 2021Cited by 10 (Europe PMC)

PMID34178995PMCIDPMC8221609DOI10.3389/fcell.2021.670913PepBankPUB-34178995

Summary

ObjectiveThe actin-sequestering proteins, thymosin beta-4 (Tβ4) and hypoxia-inducible factor (HIF)-1α, are known to be associated with angiogenesis after myocardial infarction (MI). Herein, we aimed to identify the mechanism of HIF-1α induction by Tβ4 and investigate the effects of bone marrow mesenchymal stromal cells (BMMSCs) transfected with the Tβ4 gene (TMSB4) in a rat model of MI.MethodsRat BMMSCs were isolated, cultured, and transfected with the TMSB4 gene by using the lentivirus-mediated method. Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ^{O E} ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ^{W T} ), or medium (MI). The fourth group of animals (n = 9) underwent all surgical procedures necessary for MI induction except for the ligation step (Sham). Four weeks after the injection, heart function was measured using transthoracic echocardiography. Infarct size was calculated by TTC staining, and collagen volume was measured by Masson staining. Angiogenesis in the infarcted heart area was evaluated by CD31 immunofluorescence histochemistry. In vitro experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).ResultsIn vivo experiments showed that vascular density 4 weeks after treatment was about twofold higher in BMMSC-TMSB4 ^{O E} -treated animals than in BMMSC-TMSB4 ^{W T} -treated animals (p < 0.05). The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls. Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 ^{O E} -treated animals (both p < 0.05). HIF-1α and phosphorylated HIF-1α (p-HIF-1α) in vitro were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1). The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tβ4 and further decreased with the combined treatment of Tβ4 and FG-4497 (a specific PHD inhibitor).ConclusionTMSB4-transfected BMMSCs might significantly improve recovery from myocardial ischemia and promote the generation of HIF-1α and p-HIF-1α via the AKT pathway, and inhibit the degradation of HIF-1α via the PHD and FIH pathways.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

3 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In cells in vitro, exogenous Tβ4 significantly increased HIF-1α.
In plain wordsIn cells, added Tβ4 raised HIF-1α levels.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseHIF-1α level after exogenous Tβ4
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
HIF-1α and phosphorylated HIF-1α (p-HIF-1α) in vitro were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1).
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).
Show in the study text Report a problemFND-3417899506
02LabIn vitro (cells)Mechanism
In cells in vitro, exogenous Tβ4 significantly increased phosphorylated HIF-1α.
In plain wordsIn cells, added Tβ4 raised phosphorylated HIF-1α levels.
Peptide
Thymosin beta-4 (human)
Outcome
IncreasePhosphorylated HIF-1α level after exogenous Tβ4
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
HIF-1α and phosphorylated HIF-1α (p-HIF-1α) in vitro were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1).
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).
Show in the study text Report a problemFND-3417899507
03LabIn vitro (cells)Mechanism
In cells in vitro, Tβ4 decreased expression of prolyl hydroxylase domain proteins.
In plain wordsIn cells, Tβ4 lowered the amount of prolyl hydroxylase domain proteins.
Peptide
Thymosin beta-4 (human)
Outcome
DecreasePHD protein expression after Tβ4
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tβ4 and further decreased with the combined treatment of Tβ4 and FG-4497 (a specific PHD inhibitor).
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).
Show in the study text Report a problemFND-3417899509

Studies that did not test the peptide alone7

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

04AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial infarction, TMSB4-overexpressing BMMSCs gave about twofold higher vascular density than wild-type BMMSCs.
In plain wordsIn rats with a heart attack, cells engineered to carry extra Tβ4 gene grew about twofold more blood vessels than normal cells.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseVascular density 4 weeks after treatment
Study
ratn: not reported in source
Myocardial infarction
Comparator
Wild-type BMMSCs
Outcome group
Angiogenesis · Cardiovascular
Source sentences
Summary
In vivo experiments showed that vascular density 4 weeks after treatment was about twofold higher in BMMSC-TMSB4 ^{O E} -treated animals than in BMMSC-TMSB4 ^{W T} -treated animals (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ^{O E} ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ^{W T} ), or medium (MI).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899501
05AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial infarction, cardiac function improved with both BMMSC treatments compared with controls.
In plain wordsIn rats with a heart attack, heart function improved with both cell treatments compared with controls.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseCardiac function
Study
ratn: not reported in source
Myocardial infarction
Comparator
Controls (medium)
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls.
1 context sentence(design, population, supporting numbers)
Summary · context
Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ^{O E} ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ^{W T} ), or medium (MI).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899502
06AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial infarction, infarct size improved with both BMMSC treatments compared with controls.
In plain wordsIn rats with a heart attack, infarct size improved with both cell treatments compared with controls.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseInfarct size
Study
ratn: not reported in source
Myocardial infarction
Comparator
Controls (medium)
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls.
1 context sentence(design, population, supporting numbers)
Summary · context
Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ^{O E} ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ^{W T} ), or medium (MI).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899503
07AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial infarction, the improvement in cardiac function was most prominent with TMSB4-overexpressing BMMSCs.
In plain wordsIn rats with a heart attack, heart function improved most with cells engineered to carry extra Tβ4 gene.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseCardiac function, TMSB4-overexpressing versus other groups
Study
ratn: not reported in source
Myocardial infarction
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 ^{O E} -treated animals (both p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ^{O E} ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ^{W T} ), or medium (MI).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899504
08AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In rats with myocardial infarction, the improvement in infarct size was most prominent with TMSB4-overexpressing BMMSCs.
In plain wordsIn rats with a heart attack, infarct size improved most with cells engineered to carry extra Tβ4 gene.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseInfarct size, TMSB4-overexpressing versus other groups
Study
ratn: not reported in source
Myocardial infarction
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 ^{O E} -treated animals (both p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ^{O E} ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ^{W T} ), or medium (MI).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899505
09LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In cells in vitro, the FIH promoter YC-1 blocked the Tβ4-induced increase in HIF-1α and p-HIF-1α.
In plain wordsIn cells, the compound YC-1 blocked the rise in HIF-1α that Tβ4 caused.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableTβ4-induced HIF-1α increase blocked by YC-1
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
HIF-1α and phosphorylated HIF-1α (p-HIF-1α) in vitro were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1).
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899508
10LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In cells in vitro, combined Tβ4 and the PHD inhibitor FG-4497 decreased PHD expression further.
In plain wordsIn cells, Tβ4 combined with a PHD inhibitor lowered PHD proteins further.
Peptide
Thymosin beta-4 (human)
Outcome
DecreasePHD protein expression after Tβ4 plus FG-4497
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tβ4 and further decreased with the combined treatment of Tβ4 and FG-4497 (a specific PHD inhibitor).
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3417899510

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

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