TY - JOUR
T1 - The role of focal adhesion kinase in BMP4 induction of mesenchymal stem cell adipogenesis
AU - Lee, Jeong Soon
AU - Ha, Ligyeom
AU - Kwon, Il Keun
AU - Lim, Jung Yul
N1 - Funding Information:
AO Foundation Grant ( S-10-7L ), NE DHHS Stem Cell Research Grant ( 2011-05 ), AHA Scientist Development Grant ( 12SDG12030109 ), Osteology Foundation Grant (12-006): all to Lim.
PY - 2013/6/14
Y1 - 2013/6/14
N2 - Obesity is characterized by excessive adipocytic number growth and resultant adipose tissue hyperplasia. However, molecular mechanisms of abnormal recruitment of new adipocytes from precursor cells are not fully known. Several studies showed that bone morphogenetic proteins (BMPs) also play a role in inducing mesenchymal stem cells (MSCs) to commit to adipocytes. We tested the hypothesis that focal adhesion kinase (FAK), one of the vital focal adhesion signaling molecules, is required for BMP4 induction of MSC adipogenesis. BMP4 exposure triggered FAK activation at pY397 auto-phosphorylation site in murine C3H10T1/2 MSCs. Interestingly, silencing FAK by small hairpin RNA (shRNA) significantly suppressed BMP4 induction of MSC adipogenic activities, including lipid accumulation and expression of key adipogenic genes (C/EBPα, PPARγ, aP2), as relative to shRNA vector control. As a potential molecular mechanism, BMP4-triggered phosphorylation in Smad1/5/8 and p38 was significantly downregulated by shRNA-FAK. Pharmacological FAK inhibitor 14 provided similar results in BMP4-mediated MSC adipogenesis and Smad/p38 signaling. Our data clearly suggest a link between FAK and BMP4 induction of MSC adipogenesis, and may indicate a potential therapeutic approach targeting FAK for dealing with obesity.
AB - Obesity is characterized by excessive adipocytic number growth and resultant adipose tissue hyperplasia. However, molecular mechanisms of abnormal recruitment of new adipocytes from precursor cells are not fully known. Several studies showed that bone morphogenetic proteins (BMPs) also play a role in inducing mesenchymal stem cells (MSCs) to commit to adipocytes. We tested the hypothesis that focal adhesion kinase (FAK), one of the vital focal adhesion signaling molecules, is required for BMP4 induction of MSC adipogenesis. BMP4 exposure triggered FAK activation at pY397 auto-phosphorylation site in murine C3H10T1/2 MSCs. Interestingly, silencing FAK by small hairpin RNA (shRNA) significantly suppressed BMP4 induction of MSC adipogenic activities, including lipid accumulation and expression of key adipogenic genes (C/EBPα, PPARγ, aP2), as relative to shRNA vector control. As a potential molecular mechanism, BMP4-triggered phosphorylation in Smad1/5/8 and p38 was significantly downregulated by shRNA-FAK. Pharmacological FAK inhibitor 14 provided similar results in BMP4-mediated MSC adipogenesis and Smad/p38 signaling. Our data clearly suggest a link between FAK and BMP4 induction of MSC adipogenesis, and may indicate a potential therapeutic approach targeting FAK for dealing with obesity.
KW - Adipogenesis
KW - Bone morphogenetic proteins
KW - Focal adhesion kinase
KW - Mesenchymal stem cells
KW - Obesity
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U2 - 10.1016/j.bbrc.2013.05.045
DO - 10.1016/j.bbrc.2013.05.045
M3 - Article
C2 - 23702483
AN - SCOPUS:84878960278
SN - 0006-291X
VL - 435
SP - 696
EP - 701
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -