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Thymosin β4 inhibits PDGF-BB induced activation, proliferation, and migration of human hepatic stellate cells via its actin-binding domain.

Authors :
Shah R
Reyes-Gordillo K
Rojkind M
Source :
Expert opinion on biological therapy [Expert Opin Biol Ther] 2018 Jul; Vol. 18 (sup1), pp. 177-184.
Publication Year :
2018

Abstract

Objectives: Hepatic stellate cells (HSC) trans-differentiation is central to the development of liver fibrosis, marked by the expression of pro-fibrogenic genes and the proliferation and migration of activated HSC. Therefore, preventing and/or reverting the activation, proliferation, and migration of HSC may lead to new therapies for treating fibrosis/cirrhosis. Thymosin β4 (Tβ4) inhibits PDGF-BB-induced fibrogenesis, proliferation and migration of HSC by blocking Akt phosphorylation. Here, we utilized Tβ4-derived peptides: amino-terminal-Ac-SDKPDMAEIEKFDKS (1-15aa) and actin-binding-LKKTETQ (17-23aa) to investigate the molecular mechanisms in the anti-fibrogenic actions of Tβ4.<br />Methods: We used RT-PCR, Western blot, and proliferation and migration assays in early passages of human HSC cultures treated with PDGF-BB and/or Tβ4 peptides.<br />Results: We showed that 17-23aa but not 1-15aa inhibited PDGF-BB-dependent up-regulation of PDGFβ receptor, α-SMA, and collagen 1. It also blunted the phosphorylation of Akt at T 308 and S473, resulting in the inhibition of phosphorylation of PRAS40, and HSC proliferation and migration. Interestingly, 1-15aa blocked Akt phosphorylation at S473, but not T308 by inhibiting mTOR phosphorylation, thus, it did not have any effect on HSC proliferation and migration.<br />Conclusion: These findings suggest that while 1-15aa has a minor effect on Akt phosphorylation, the anti-fibrogenic actions of Tβ4 are exerted via 17-23aa.

Details

Language :
English
ISSN :
1744-7682
Volume :
18
Issue :
sup1
Database :
MEDLINE
Journal :
Expert opinion on biological therapy
Publication Type :
Academic Journal
Accession number :
30063851
Full Text :
https://doi.org/10.1080/14712598.2018.1478961