Role of c-Jun N-terminal kinase in the PDGF-induced proliferation and migration of human adipose tissue-derived mesenchymal stem cells.
Platelet-derived growth factor (PDGF) is a critical regulator of proliferation and migration for mesenchymal type cells. In this study, we examined the role of mitogen-activated protein (MAP) kinases in the PDGF-BB-induced proliferation and migration of human adipose tissue-derived mesenchymal stem cells (hATSCs). The PDGF-induced proliferation was prevented by a pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor, SP600125. However, it was not prevented by a pretreatment with a p38 MAP kinase inhibitor, SB202190, and a specific inhibitor of the upstream kinase of extracellular signal-regulated kinase (ERK1/2), U0126. Treatment with PDGF induced the activation of JNK and ERK in hATSCs, and pretreatment with SP600125 specifically inhibited the PDGF-induced activation of JNK. Treatment with PDGF induced the cell cycle transition from the G0/G1 phase to the S phase, the elevated expression of cyclin D1, and the phosphorylation of Rb, which were prevented by a pretreatment with SP600125. In addition, the PDGF-induced migration of hATSCs was completely blocked by a pretreatment with SP600125, but not with U0126 and SB202190. These results suggest that JNK protein kinase plays a key role in the PDGF-induced proliferation and migration of mesenchymal stem cells.
Kang
Yong Jung
YJ
Department of Physiology, Medical Research Institute, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea.
Jeon
Eun Su
ES
Song
Hae Young
HY
Woo
Jae Suk
JS
Jung
Jin Sup
JS
Kim
Yong Keun
YK
Kim
Jae Ho
JH
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D013997:Time Factors
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019938:Cyclin D1; D000077214:Becaplermin; D048031:JNK Mitogen-Activated Protein Kinases