Thymosin beta-4 regulates activation of hepatic stellate cells via hedgehog signaling.

Kim J, Hyun J, Wang S, Lee C, Lee JW, Moon EY, Cha H, Diehl AM, Jung Y

Scientific reports19 Jun 2017Cited by 19 (Europe PMC)

PMID28630423PMCIDPMC5476572DOI10.1038/s41598-017-03782-xPepBankPUB-28630423

Summary

The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2. A TB4 CRISPR also blocked the activation of primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontargeting control CRISPR. Double immunostaining and an immunoprecipitation assay revealed that TB4 interacted with either smoothened at the cytoplasm or GLI2 at the nucleus in LX-2. Smoothened suppression in primary HSCs using a Hh antagonist or adenovirus transduction decreased TB4 expression with the reduced activation of HSCs. Tb4-overexpressing transgenic mice treated with CCl₄ were susceptible to the development hepatic fibrosis with higher levels of ILK, pGSK3b, and Hh activity, as compared with wild-type mice. These findings demonstrate that TB4 regulates HSC activation by influencing the activity of Smoothened and GLI2, suggesting TB4 as a novel therapeutic target in liver disease.

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

Results from this study13

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

Studies that did not test the peptide alone13

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 Tb4-overexpressing transgenic mice given CCl4, hepatic fibrosis developed more readily with higher ILK, pGSK3b and Hh activity than in wild-type mice.
In plain wordsIn mice bred to make extra TB4, liver damage from a toxin led to more scarring than in normal mice.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseHepatic fibrosis susceptibility in Tb4-overexpressing mice
Study
mousen: not reported in source
Tb4-overexpressing transgenic mice with CCl4
Comparator
Wild-type mice
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
Tb4-overexpressing transgenic mice treated with CCl₄ were susceptible to the development hepatic fibrosis with higher levels of ILK, pGSK3b, and Hh activity, as compared with wild-type mice.
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-2863042313
02LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In LX-2 hepatic stellate cells, TB4 siRNA reduced hepatic stellate cell functions.
In plain wordsIn cells, switching off TB4 reduced the activity of liver scar-forming cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseHSC functions after TB4 siRNA
Study
n: not reported in source
LX-2 hepatic stellate cells
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
HSC functions declined in a TB4 siRNA-treated LX-2.
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-2863042301
03LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In LX-2 cells, TB4 suppression down-regulated integrin linked kinase.
In plain wordsIn cells, switching off TB4 lowered the level of a signalling protein (ILK).
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseILK expression after TB4 suppression
Study
n: not reported in source
LX-2 hepatic stellate cells
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2.
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-2863042302
04LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In LX-2 cells, TB4 suppression down-regulated phosphorylated GSK-3B.
In plain wordsIn cells, switching off TB4 lowered the level of a signalling protein (pGSK-3B).
Peptide
Thymosin beta-4 (human)
Outcome
DecreasepGSK-3B after TB4 suppression
Study
n: not reported in source
LX-2 hepatic stellate cells
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2.
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-2863042303
05LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In LX-2 cells, TB4 suppression decreased smoothened expression.
In plain wordsIn cells, switching off TB4 lowered the level of a signalling protein (smoothened).
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseSmoothened expression after TB4 suppression
Study
n: not reported in source
LX-2 hepatic stellate cells
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2.
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-2863042304
06LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In LX-2 cells, TB4 suppression decreased GLI2 expression.
In plain wordsIn cells, switching off TB4 lowered the level of a signalling protein (GLI2).
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseGLI2 expression after TB4 suppression
Study
n: not reported in source
LX-2 hepatic stellate cells
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2.
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-2863042305
07LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In primary hepatic stellate cells, TB4 CRISPR blocked activation compared with nontargeting control CRISPR.
In plain wordsIn cells, removing TB4 stopped liver scar-forming cells from becoming active, compared with a control.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseActivation of primary HSCs after TB4 CRISPR
Study
n: not reported in source
primary hepatic stellate cells
Comparator
Nontargeting control CRISPR
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
A TB4 CRISPR also blocked the activation of primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontargeting control CRISPR.
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-2863042306
08LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In primary hepatic stellate cells, TB4 CRISPR decreased smoothened expression compared with nontargeting control CRISPR.
In plain wordsIn cells, removing TB4 lowered smoothened compared with a control.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseSmoothened expression after TB4 CRISPR
Study
n: not reported in source
primary hepatic stellate cells
Comparator
Nontargeting control CRISPR
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
A TB4 CRISPR also blocked the activation of primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontargeting control CRISPR.
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-2863042307
09LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In primary hepatic stellate cells, TB4 CRISPR decreased GLI2 expression compared with nontargeting control CRISPR.
In plain wordsIn cells, removing TB4 lowered GLI2 compared with a control.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseGLI2 expression after TB4 CRISPR
Study
n: not reported in source
primary hepatic stellate cells
Comparator
Nontargeting control CRISPR
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
A TB4 CRISPR also blocked the activation of primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontargeting control CRISPR.
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-2863042308
10LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In primary hepatic stellate cells, TB4 CRISPR decreased ILK expression compared with nontargeting control CRISPR.
In plain wordsIn cells, removing TB4 lowered ILK compared with a control.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseILK expression after TB4 CRISPR
Study
n: not reported in source
primary hepatic stellate cells
Comparator
Nontargeting control CRISPR
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
A TB4 CRISPR also blocked the activation of primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontargeting control CRISPR.
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-2863042309
11LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In LX-2 cells, TB4 interacted with smoothened in the cytoplasm and with GLI2 in the nucleus.
In plain wordsIn cells, TB4 physically interacted with two signalling proteins, smoothened and GLI2.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableTB4 interaction with smoothened and GLI2
Study
n: not reported in source
LX-2 hepatic stellate cells
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
Double immunostaining and an immunoprecipitation assay revealed that TB4 interacted with either smoothened at the cytoplasm or GLI2 at the nucleus in LX-2.
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-2863042310
12LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In primary hepatic stellate cells, suppressing smoothened decreased TB4 expression.
In plain wordsIn cells, blocking smoothened lowered TB4 levels.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTB4 expression after smoothened suppression
Study
n: not reported in source
primary hepatic stellate cells
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
Smoothened suppression in primary HSCs using a Hh antagonist or adenovirus transduction decreased TB4 expression with the reduced activation of HSCs.
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-2863042311
13LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In primary hepatic stellate cells, suppressing smoothened reduced activation.
In plain wordsIn cells, blocking smoothened reduced activation of liver scar-forming cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseHepatic stellate cell activation after smoothened suppression
Study
n: not reported in source
primary hepatic stellate cells
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
Smoothened suppression in primary HSCs using a Hh antagonist or adenovirus transduction decreased TB4 expression with the reduced activation of HSCs.
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-2863042312

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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