The role of focal adhesion kinase in BMP4 induction of mesenchymal stem cell adipogenesis

Jeong Soon Lee, Ligyeom Ha, Il Keun Kwon, Jung Y Lim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)696-701
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume435
Issue number4
DOIs
StatePublished - Jun 14 2013

Fingerprint

Adipogenesis
Focal Adhesion Protein-Tyrosine Kinases
Stem cells
Mesenchymal Stromal Cells
Small Interfering RNA
Phosphorylation
Adipocytes
Obesity
Bone Morphogenetic Proteins
Peroxisome Proliferator-Activated Receptors
Focal Adhesions
Hyperplasia
Adipose Tissue
Down-Regulation
Adhesion
Genes
Chemical activation
Pharmacology
Tissue
Lipids

Keywords

  • Adipogenesis
  • Bone morphogenetic proteins
  • Focal adhesion kinase
  • Mesenchymal stem cells
  • Obesity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The role of focal adhesion kinase in BMP4 induction of mesenchymal stem cell adipogenesis. / Lee, Jeong Soon; Ha, Ligyeom; Kwon, Il Keun; Lim, Jung Y.

In: Biochemical and Biophysical Research Communications, Vol. 435, No. 4, 14.06.2013, p. 696-701.

Research output: Contribution to journalArticle

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