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

胸腺肽 β4 通过其肌动蛋白结合域抑制 PDGF-BB 诱导的人类肝星状细胞的活化、增殖和迁移

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作者:Ruchi Shah, Karina Reyes-Gordillo, Marcos Rojkind

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.

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.

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.

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