ArticleThe American journal of pathology2011
Thymosin-β4 (Tβ4) blunts PDGF-dependent phosphorylation and binding of AKT to actin in hepatic stellate cells.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Post-translational modifications of collagen and its related diseases in metabolic pathways.Acta pharmaceutica Sinica. B · 2025Review
- Metabolomic Profiling and Network Toxicology: Mechanistic Insights into Effect of Gossypol Acetate Isomers in Uterine Fibroids and Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2024Article
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- The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis.International journal of molecular sciences · 2022Review
- Progress on the Function and Application of Thymosin β4.Frontiers in endocrinology · 2021Review
- Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway.Apoptosis : an international journal on programmed cell death · 2020Article
- Article
- Stevioside inhibits experimental fibrosis by down-regulating profibrotic Smad pathways and blocking hepatic stellate cell activation.Basic & clinical pharmacology & toxicology · 2019Article
- Antioxidant and immunomodulatory activity induced by stevioside in liver damage: In vivo, in vitro and in silico assays.Life sciences · 2019Article
- Thymosin β4 inhibits PDGF-BB induced activation, proliferation, and migration of human hepatic stellate cells via its actin-binding domain.Expert opinion on biological therapy · 2018Article
- ThymosinOxidative medicine and cellular longevity · 2018Article
- Article
- Potential role of thymosin beta 4 in the treatment of nonalcoholic fatty liver disease.Chronic diseases and translational medicine · 2017Review
- Effects of exogenous thymosin β4 on carbon tetrachloride-induced liver injury and fibrosis.Scientific reports · 2017Article
- Comparative proteomics of paired vocal fold and oral mucosa fibroblasts.Journal of proteomics · 2017Article
- Potential role of thymosin Beta 4 in liver fibrosis.International journal of molecular sciences · 2015Review
- Article
- Novel modulators of hepatosteatosis, inflammation and fibrogenesis.Hepatology international · 2014Article
- Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.PloS one · 2014Article
- Thymosin β4 and its degradation product, Ac-SDKP, are novel reparative factors in renal fibrosis.Kidney international · 2013Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic stellate cell transdifferentiation is a key event in the fibrogenic cascade. Therefore, attempts to prevent and/or revert the myofibroblastic phenotype could result in novel therapeutic approaches to treat liver cirrhosis. The expression of platelet-derived growth factor (PDGF)-β receptor and the proliferative response to platelet-derived growth factor-ββ (PDGF-ββ) are hallmarks of the transdifferentiation of hepatic stellate cells (HSC). In this communication, we investigated whether thymosin-β4 (Tβ4), a chemokine expressed by HSC could prevent PDGF-BB-mediated proliferation and migration of cultured HSC. Using early passages of human HSC, we showed that Tβ4 inhibited cell proliferation and migration and prevented the expression of PDGF-β receptor (PDGF-βr), α-smooth muscle actin and α1(I) collagen mRNAs. Tβ4 also inhibited the reappearance of PDGF-βr after its PDGF-BB-dependent degradation. These PDGF-dependent events were associated with the inhibition of AKT phosphorylation at both T308 and S473 amino acid residues. The lack of AKT phosphorylation was not due to the inhibition of PDGF-βr phosphorylation, the activation of phosphoinositide 3-kinase (PI3K), pyruvate dehydrogenase kinase isozyme 1 (PDK1), and mammalian target of rapamycin (mTOR). We found that PDGF-BB induced AKT binding to actin, and that Tβ4 prevented this effect. Tβ4 also prevented the activation of freshly isolated HSC cultured in the presence of Dulbecco's modified Eagle's medium or Dulbecco's minimal essential medium containing 10% fetal bovine serum. In conclusion, overall, our findings suggest that Tβ4 by sequestering actin prevents binding of AKT, thus inhibiting its phosphorylation. Therefore, Tβ4 has the potential to be an antifibrogenic agent.
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