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The small peptide OGP(10-14) reduces proliferation and induces differentiation of TPO-primed M07-e cells through RhoA/TGFbeta1/SFK pathway
No full textBackground: Osteogenic growth peptide (OGP) is a 14-mer peptide found in relevant concentration in blood, and its carboxy-terminal fragment [OGP(10-14)] represents the active portion of the full-length peptide. In addition to stimulating bone formation, OGP(10-14) shows hematological activity. In fact, it highly enhances hematopoiesis-affecting stem progenitors. Moreover, OGP(10-14) reduces the growth and induces the differentiation of the hematological tumour cell line trombophoietin(TPO)- primed M07-e by interfering with RhoA and Src kinase pathways. In the present report, we went deeper into this mechanism and evaluated the possible interference of the OGP(10-14) signal pathway with TGFß1 and TPO receptor Mpl. Material/Methods: In OGP(10-14)-treated M07-e cells cultured with or without RhoA and Src kinases inhibitors (C3 and PP2), expression of TGFß1, Mpl, and Src kinases was analyzed by immunoperoxidase technique. Activated RhoA expression was studied using the G-LISATM quantitative test. Results: In M07-e cells, both OGP(10-14) and PP2 activate RhoA, inhibit Src kinases, reduce Mpl expression and increase TGFß1 expression. OGP(10-14) and PP2 show the same behavior, causing an additive effect when associated. Conclusions: OGP(10-14) induces TPO-primed M07-e cells differentiation through RhoA/TGFß1/SFKs signaling pathway. In particular OGP(10-14) acts as a Src inhibitor, showing the same effects of PP2
The small peptide OGP(10-14) acts through Src kinases and RhoA pathways in Mo-7e cells: morphologic and immunologic evaluation
No full textAbstract
BACKGROUND:
Osteogenic growth peptide (OGP) is an endogenous tetradecapeptide present in micromolar concentrations in mammalian serum; its carboxy-terminal pentapeptide, OGP(10-14), represents its physiologically active fragment. OGP(10-14) induces proliferation and differentiation in fibroblast and osteoblast cell lines, and it enhances hematopoiesis in vitro and in vivo. The signaling pathways triggered by OGP(10-14) are not yet fully known. In the present report, we evaluated the effect of OGP(10-14) on differentiation of a cancer megakaryoblast cell line and its involvement on RhoA and Src family kinases signaling pathway.
MATERIAL/METHODS:
Cell proliferation of the Mo-7e line was evaluated using the MTT test. Mo-7e differentiation was evaluated by microscopic observation of cell morphology and by expression of the factor VIII-related antigen. Involvement of RhoA and Src kinases on signaling pathways triggered by OGP(10-14) was analyzed using RhoA and Src family kinase (SFK) inhibitors (C3 and PP2) and an immunoperoxidase technique.
RESULTS:
OGP(10-14) induces expression of the factor VIII-related antigen, morphologic changes indicative of megakaryocytic differentiation, and a down-regulation of the Fyn Src kinase. These OGP(10-14) effects were prevented by C3 and enhanced by PP2.
CONCLUSIONS:
The anti-proliferative and pro-differentiating activities of OGP(10-14) on thrombopoietin (TPO)-primed Mo-7e cells are mediated by RhoA and Src kinase pathways as demonstrated by the use of C3 and PP2
WT1 GENE EXPRESSION IS SIGNIFICANTLY INHIBITED BY VORINOSTAT AND BORTEZOMIB IN MYELOPROLIFERATIVE/MYELODISPLASTIC DISEASES
No full textRhoA activation in renal proximal tubules: its role in cellular pathogenetic dynamics of IgA nephropathy fibrosis.
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No full textInhibition of RhoA activation in human bronchial smooth muscle cells: novel insights into the molecular mechanism of salbutamol action
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The HPRG-like protein associated to AMP deaminase is not synthesized in skeletal muscle but it is acquired from plasma
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