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KMID : 0811720160200050459
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Korean Journal of Physiology & Pharmacology
2016 Volume.20 No. 5 p.459 ~ p.466
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Lnk is an important modulator of insulin-like growth factor-1/Akt/peroxisome proliferator-activated receptor-gamma axis during adipogenesis of mesenchymal stem cells
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Lee Jun-Hee
Lee Sang-Hun
Lee Hyang-Seon
Ji Seung-Taek
Jung Seok-Yun
Kim Jae-Ho
Bae Sun-Sik
Kwon Sang-Mo
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Abstract
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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 proliferatoractivated 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.
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KEYWORD
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Adipogenesis, Insulin-like growth factor-1, Lnk, Mesenchymal stem cell, Peroxisome proliferator-activated, receptors gamma
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