Effects of leukemia inhibitory factor receptor on the adipogenic differentiation of human bone marrow mesenchymal stem cells

Mol Med Rep. 2019 Jun;19(6):4719-4726. doi: 10.3892/mmr.2019.10140. Epub 2019 Apr 8.

Abstract

Leukemia inhibitory factor (LIF) modulates various biological processes. Although previous studies have described the effects of LIF on adipocyte differentiation, the role of LIF receptor (LIFR) on adipocyte differentiation remains unclear. Using reverse transcription‑quantitative PCR (RT‑qPCR), LIFR expression was demonstrated to increase during adipogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs), indicating that LIFR may be involved in this process. To further evaluate the association between LIFR and adipogenic differentiation, lentivirus‑mediated LIFR knockdown was performed in hMSCs. Cells were divided into two groups: Negative control group and LIFR‑knockdown group. During the adipogenic differentiation process, intracellular lipid accumulation was assessed with Oil Red O staining at various time points (days 3, 6 and 9). Additionally, the mRNA and protein expression levels of LIF, LIFR and three molecular indicators of adipogenesis, peroxisome proliferator‑activated receptor γ (PPARγ), CCAAT enhancer binding protein α (C/EBPα) and fatty acid binding protein 4 (FABP4/aP2), were assessed by RT‑qPCR and western blotting. The culture supernatant was collected to evaluate the concentration of LIF using ELISA. The present results suggested that LIFR expression progressively increased during adipogenic differentiation of hMSCs. Conversely, LIFR knockdown significantly suppressed this process. Additionally, PPARγ, C/EBPα and aP2 were inhibited following LIFR knockdown. In contrast with LIFR, the expression levels of LIF were significantly decreased after the initiation of adipogenic differentiation. Therefore, the expression levels of LIF and LIFR exhibited opposite trends. Collectively, the present results suggested that LIFR promoted adipogenic differentiation, whereas LIF may negatively regulate this process.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipogenesis / genetics
  • Adipogenesis / physiology*
  • Bone Marrow Cells
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • Humans
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism
  • Leukemia Inhibitory Factor Receptor alpha Subunit / genetics
  • Leukemia Inhibitory Factor Receptor alpha Subunit / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Mesenchymal Stem Cells / physiology*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • RNA, Messenger / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • LIF protein, human
  • LIFR protein, human
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • PPAR gamma
  • RNA, Messenger