Lnk is an important modulator of insulin-like growth factor-1/Akt/peroxisome proliferator-activated receptor-gamma axis during adipogenesis of mesenchymal stem cells.
Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than Lnk (-/-) MSCs. An ex vivo adipogenic differentiation assay showed that Lnk (-/-) MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma (PPAR-γ) and its adipogenic target genes (LPL and FABP4) significantly decreased in Lnk (-/-) MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the IGF-1/Akt/PPAR-γ pathway.
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jun Hee
JH
Lee
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea.; Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Korea.
Sang Hun
SH
Lee
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
Hyang Seon
HS
Lee
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
Seung Taek
ST
Ji
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
Seok Yun
SY
Jung
Department of Physiology, Pusan Natinoal University, Yangsan 50612, Korea.; Research Institute of Convergence Biomedical Science and Technology, Pusan National University, Yangsan Hospital, Yangsan 50612, Korea.
Jae Ho
JH
Kim
Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea.
Sun Sik
SS
Bae
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
Sang-Mo
SM
Kwon
Adipogenesis; Insulin-like growth factor-1; Lnk; Mesenchymal stem cell; Peroxisome proliferator-activated; receptors gamma