Thrombin peptide (TP508) promotes adipose tissue-derived stem cell proliferation via PI3 kinase/Akt pathway.
A synthetic peptide representing the receptor-binding domain of human thrombin (TP508) promotes angiogenesis and accelerates wound healing in animal models. However, the mechanisms underlying the therapeutic effects of TP508 have not been clearly defined. In this study, we set out to determine whether TP508 could stimulate stem cell proliferation. Adipose tissue-derived stem cells (ASCs) were incubated with TP508 (5 microg/ml) and cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation. Our data showed that TP508 treatment significantly stimulated BrdU incorporation in ASCs (p < 0.01). The increased BrdU incorporation induced by TP508 was abolished by the PI3 kinase (PI3K) inhibitor LY294002 at 50 microM. Western blot analysis of ASCs revealed increased phosphorylation of Akt in response to TP508 when compared to unstimulated controls. These results indicate that TP508 exerts proliferative effects on ASCs via the PI3K/Akt pathway.
Freyberg
Susanne
S
Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex. 77054, USA.
Song
Yao-Hua
YH
Muehlberg
Fabian
F
Alt
Eckhard
E
D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects* / Q000201:enzymology; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000201:enzymology; D013917:Thrombin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
D001973:Bromodeoxyuridine; D002867:Chromones; D009025:Morpholines; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018179:Receptors, Thrombin; D013917:Thrombin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C412222:rusalatide acetate