Premium
The Actin Binding domain of Thymosin β 4 blunts PDGF‐dependent phosphorylation and binding of Akt to Actin in Hepatic Stellate Cells
Author(s) -
Shah Ruchi,
ReyesGordillo Karina,
Rojkind Marcos
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.366.5
Thymosin β4 (Tβ4), inhibits hepatic stellate cell (HSC) proliferation and migration. It also blocks the expression of PDGF‐β receptor and α‐SMA in HSC treated with PDGF‐BB by preventing phosphorylation and binding of Akt to actin. Tβ4 has several peptide domains that could reproduce some Tβ4‐mediated events. Thus, we investigated if the Tβ4‐derived peptide that binds to actin (LKKTETQ)(Tβ17‐23) could be responsible for the Tβ4‐dependent inhibition of HSC activation. METHODS Human HSC (passage 4–7) were treated with PDGF‐BB (50ng/mL) in the presence or absence of 10ng/mL of Tβ17‐23. Cell proliferation was determined by MTT and cell migration was analyzed by a wound healing assay. Expression of several protein kinases was determined by Western analysis and the expression of PDGF‐βR, α1(I) collagen and α‐SMA mRNA was determined by qPCR. RESULTS Tβ17‐23 inhibited PDGF‐BB‐dependent HSC proliferation and migration and also the expression of PDGF‐βR, α1(I) collagen and α‐SMA mRNAs. In addition, Tβ17‐23 blunted PDGF‐BB‐dependent phosphorylation of AKT (T308, S473) but not pPTEN, pPDK1, p‐mTOR and p85PI3K. CONCLUSION Because Tβ17‐23 corresponds to the Tβ4 actin‐binding domain we speculate that Tβ417‐23 binds to actin and through this mechanism it prevents the PDGF‐BB‐induced binding and phosphorylation of AKT, thus resulting in the inhibition of HSC proliferation and migration. Supported by grant AA 010541.