Targeted Deletion of Thymosin Beta 4 in Hepatic Stellate Cells Ameliorates Liver Fibrosis in a Transgenic Mouse Model.

Kim J, Lee C, Han J, Jeong H, Wang S, Choi YH, Jung Y

Cells18 Jun 2023Cited by 2 (Europe PMC)

PMID37371128PMCIDPMC10297343DOI10.3390/cells12121658PepBankPUB-37371128

Summary

Liver fibrosis is the most common feature of liver disease, and activated hepatic stellate cells (HSCs) are the main contributors to liver fibrosis. Thus, finding key targets that modulate HSC activation is important to prevent liver fibrosis. Previously, we showed that thymosin β4 (Tβ4) influenced HSC activation by interacting with the Hedgehog pathway in vitro. Herein, we generated Tβ4 conditional knockout (Tβ4-flox) mice to investigate in vivo functions of Tβ4 in liver fibrosis. To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis. Tβ4 was selectively suppressed in the activated HSCs of DTG mouse liver, and this reduction attenuated liver injury, including fibrosis, in both fibrotic models by repressing Hedgehog (Hh) signaling. In addition, the re-expression of Tβ4 by an adeno-associated virus reversed the effect of HSC-specific Tβ4 deletion and led to liver fibrosis with Hh activation in CCl₄-exposed mice treated with tamoxifen. In conclusion, our results demonstrate that Tβ4 is a crucial regulator of HSC activation, suggesting it as a novel therapeutic target for curing liver fibrosis.

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

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

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).

01AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In double-transgenic mice, Tβ4 was selectively suppressed in activated hepatic stellate cells of the liver.
In plain wordsIn mice, thymosin β4 was switched off only in liver scar-forming cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTβ4 level in activated HSCs after deletion
Study
mousen: not reported in source
Tβ4 conditional knockout in activated HSCs (double-transgenic mice)
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
Tβ4 was selectively suppressed in the activated HSCs of DTG mouse liver
1 context sentence(design, population, supporting numbers)
Summary · context
To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis.
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-3737112801
02AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In CCl4-exposed mice, deleting Tβ4 in activated hepatic stellate cells attenuated liver injury, including fibrosis.
In plain wordsIn mice with chemically induced liver scarring, removing thymosin β4 from scar-forming cells reduced liver damage.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseLiver injury and fibrosis in CCl4 model after HSC Tβ4 deletion
Study
mousen: not reported in source
CCl4-induced liver fibrosis, HSC-specific Tβ4 knockout
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
this reduction attenuated liver injury, including fibrosis, in both fibrotic models
1 context sentence(design, population, supporting numbers)
Summary · context
To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis.
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-3737112802
03AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In mice with bile duct ligation, deleting Tβ4 in activated hepatic stellate cells attenuated liver injury, including fibrosis.
In plain wordsIn mice with bile duct ligation, removing thymosin β4 from scar-forming cells reduced liver damage.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseLiver injury and fibrosis in BDL model after HSC Tβ4 deletion
Study
mousen: not reported in source
Bile duct ligation liver fibrosis, HSC-specific Tβ4 knockout
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
this reduction attenuated liver injury, including fibrosis, in both fibrotic models
1 context sentence(design, population, supporting numbers)
Summary · context
To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis.
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-3737112803
04AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In mice with HSC-specific Tβ4 deletion, Hedgehog (Hh) signaling was repressed in both fibrotic models.
In plain wordsIn mice, removing thymosin β4 from scar-forming cells turned down a signal pathway linked to liver scarring.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseHedgehog signaling after HSC Tβ4 deletion
Study
mousen: not reported in source
Tβ4 conditional knockout in activated HSCs (double-transgenic mice)
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
by repressing Hedgehog (Hh) signaling.
1 context sentence(design, population, supporting numbers)
Summary · context
To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis.
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-3737112804
05AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In CCl4-exposed knockout mice treated with tamoxifen, AAV re-expression of Tβ4 reversed the effect of the deletion and led to liver fibrosis.
In plain wordsIn mice, putting thymosin β4 back reversed the benefit of removing it and brought liver scarring back.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseLiver fibrosis after Tβ4 re-expression
Study
mousen: not reported in source
CCl4-exposed HSC-specific Tβ4 knockout mice treated with tamoxifen
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
In addition, the re-expression of Tβ4 by an adeno-associated virus reversed the effect of HSC-specific Tβ4 deletion and led to liver fibrosis with Hh activation in CCl₄-exposed mice treated with tamoxifen.
1 context sentence(design, population, supporting numbers)
Summary · context
To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis.
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-3737112805
06AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In CCl4-exposed knockout mice treated with tamoxifen, AAV re-expression of Tβ4 led to Hh activation along with liver fibrosis.
In plain wordsIn mice, putting thymosin β4 back switched the liver-scarring signal pathway on again.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseHedgehog activation after Tβ4 re-expression
Study
mousen: not reported in source
CCl4-exposed HSC-specific Tβ4 knockout mice treated with tamoxifen
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
In addition, the re-expression of Tβ4 by an adeno-associated virus reversed the effect of HSC-specific Tβ4 deletion and led to liver fibrosis with Hh activation in CCl₄-exposed mice treated with tamoxifen.
1 context sentence(design, population, supporting numbers)
Summary · context
To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ER^T2 mice, and these mice were administered carbon tetrachloride (CCl₄) or underwent bile duct ligation to induce liver fibrosis.
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-3737112806

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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