Significance of thymosin β4 and implication of PINCH-1-ILK-α-parvin (PIP) complex in human dilated cardiomyopathy.

Sopko N, Qin Y, Finan A, Dadabayev A, Chigurupati S, Qin J, Penn MS, Gupta S

PloS one19 May 2011Cited by 48 (Europe PMC)

PMID21625516PMCIDPMC3098280DOI10.1371/journal.pone.0020184PepBankPUB-21625516

Summary

Myocardial remodeling is a major contributor in the development of heart failure (HF) after myocardial infarction (MI). Integrin-linked kinase (ILK), LIM-only adaptor PINCH-1, and α-parvin are essential components of focal adhesions (FAs), which are highly expressed in the heart. ILK binds tightly to PINCH-1 and α-parvin, which regulates FA assembly and promotes cell survival via the activation of the kinase Akt. Mice lacking ILK, PINCH or α-parvin have been shown to develop severe defects in the heart, suggesting that these proteins play a critical role in heart function. Utilizing failing human heart tissues (dilated cardiomyopathy, DCM), we found a 2.27-fold (p<0.001) enhanced expression of PINCH, 4 fold for α-parvin, and 10.5 fold (p<0.001) for ILK as compared to non-failing (NF) counterparts. No significant enhancements were found for the PINCH isoform PINCH-2 and parvin isoform β-parvin. Using a co-immunoprecipitation method, we also found that the PINCH-1-ILK-α-parvin (PIP) complex and Akt activation were significantly up-regulated. These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model. Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis. In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI. These data suggest that the PIP complex and activation of Akt play critical roles in HF development. Tβ4 treatment likely improves cardiac function by enhancing PIP mediated Akt activation and suppressing NF-κB activation and collagen-mediated fibrosis. These data provide significant insight into the role of the PIP-Akt pathway and its regulation by Tβ4 treatment in post-MI.

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

Results from this study5

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

01AnimalAnimal study (in vivo)Mechanism
In mouse models of myocardial infarction and transaortic constriction, Tβ4 further enhanced the level of PINCH-1-ILK-alpha-parvin complex components.
In plain wordsIn mice with heart injury, thymosin beta‑4 raised the level of the PIP protein complex further.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseLevel of PIP complex components
Study
mousen: not reported in source
Mouse myocardial infarction (MI) and transaortic constriction (TAC) models
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model.
Show in the study text Report a problemFND-2162551601
02AnimalAnimal study (in vivo)Mechanism
In mouse models of myocardial infarction and transaortic constriction, Tβ4 further enhanced Akt activation.
In plain wordsIn mice with heart injury, thymosin beta‑4 raised Akt activation further.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseAkt activation
Study
mousen: not reported in source
Mouse myocardial infarction (MI) and transaortic constriction (TAC) models
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model.
Show in the study text Report a problemFND-2162551602
03AnimalAnimal study (in vivo)Mechanism
In mouse models of myocardial infarction and transaortic constriction, Tβ4 substantially suppressed NF-kB activation.
In plain wordsIn mice with heart injury, thymosin beta‑4 strongly reduced NF-kB activation.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseNF-kB activation
Study
mousen: not reported in source
Mouse myocardial infarction (MI) and transaortic constriction (TAC) models
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model.
Show in the study text Report a problemFND-2162551603
04AnimalAnimal study (in vivo)Mechanism
In mouse models of myocardial infarction and transaortic constriction, Tβ4 substantially suppressed collagen expression.
In plain wordsIn mice with heart injury, thymosin beta‑4 strongly reduced collagen expression.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseCollagen expression
Study
mousen: not reported in source
Mouse myocardial infarction (MI) and transaortic constriction (TAC) models
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model.
Show in the study text Report a problemFND-2162551604
05AnimalAnimal study (in vivo)Efficacy outcome
In mice with myocardial infarction given the Akt inhibitor wortmannin, Tβ4 had a decreased effect in protecting the heart.
In plain wordsIn mice with heart attack, blocking Akt with wortmannin made thymosin beta‑4 protect the heart less.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableHeart protection from MI with Akt inhibitor wortmannin
Study
mousen: not reported in source
Mouse myocardial infarction (MI) and transaortic constriction (TAC) models
Comparator
Tβ4 without wortmannin
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI.
1 context sentence(design, population, supporting numbers)
Summary · context
These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model.
Show in the study text Report a problemFND-2162551605

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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