Effect of growth factors on the proliferation and gene expression of human meibomian gland epithelial cells

Shaohui Liu, Wendy R. Kam, Juan Ding, Mark P. Hatton, David A. Sullivan

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

PURPOSE. We hypothesize that growth factors, including epidermal growth factor (EGF) and bovine pituitary extract (BPE), induce proliferation, but not differentiation (e.g., lipid accumulation), of human meibomian gland epithelial cells. We also hypothesize that these actions involve a significant upregulation of genes linked to cell cycle processes, and a significant downregulation of genes associated with differentiation. Our objective was to test these hypotheses. METHODS. Immortalized human meibomian gland and conjunctival epithelial cells were cultured for varying time periods in the presence or absence of EGF, BPE, EGF {thorn} BPE, or serum, followed by cell counting, neutral lipid staining, or RNA isolation for molecular biological procedures. RESULTS. Our studies show that growth factors stimulate a significant, time-dependent proliferation of human meibomian gland epithelial cells. These effects are associated with a significant upregulation of genes linked to cell cycle, DNA replication, ribosomes, and translation, and a significant decrease in those related to cell differentiation, tissue development, lipid metabolic processes, and peroxisome proliferator-activated receptor signaling. Serum-induced differentiation, but not growth factor-related proliferation, elicits a pronounced lipid accumulation in human meibomian gland epithelial cells. This lipogenic response is unique, and is not duplicated by human conjunctival epithelial cells. CONCLUSIONS. Our results demonstrate that EGF and BPE stimulate human meibomian gland epithelial cells to proliferate. Further, our findings show that action is associated with an upregulation of cell cycle and translation ontologies, and a downregulation of genetic pathways linked to differentiation and lipid biosynthesis.

Original languageEnglish (US)
Pages (from-to)2541-2550
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number4
DOIs
StatePublished - Apr 15 2013
Externally publishedYes

Fingerprint

Meibomian Glands
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Gene Expression
Epidermal Growth Factor
Lipids
Cell Cycle
Up-Regulation
Down-Regulation
Growth Differentiation Factors
Genes
Peroxisome Proliferator-Activated Receptors
Serum
DNA Replication
Ribosomes
Cell Differentiation
RNA
Staining and Labeling

Keywords

  • Gene expression
  • Growth factors
  • Meibomian gland

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Effect of growth factors on the proliferation and gene expression of human meibomian gland epithelial cells. / Liu, Shaohui; Kam, Wendy R.; Ding, Juan; Hatton, Mark P.; Sullivan, David A.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 4, 15.04.2013, p. 2541-2550.

Research output: Contribution to journalArticle

Liu, Shaohui ; Kam, Wendy R. ; Ding, Juan ; Hatton, Mark P. ; Sullivan, David A. / Effect of growth factors on the proliferation and gene expression of human meibomian gland epithelial cells. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 4. pp. 2541-2550.
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AB - PURPOSE. We hypothesize that growth factors, including epidermal growth factor (EGF) and bovine pituitary extract (BPE), induce proliferation, but not differentiation (e.g., lipid accumulation), of human meibomian gland epithelial cells. We also hypothesize that these actions involve a significant upregulation of genes linked to cell cycle processes, and a significant downregulation of genes associated with differentiation. Our objective was to test these hypotheses. METHODS. Immortalized human meibomian gland and conjunctival epithelial cells were cultured for varying time periods in the presence or absence of EGF, BPE, EGF {thorn} BPE, or serum, followed by cell counting, neutral lipid staining, or RNA isolation for molecular biological procedures. RESULTS. Our studies show that growth factors stimulate a significant, time-dependent proliferation of human meibomian gland epithelial cells. These effects are associated with a significant upregulation of genes linked to cell cycle, DNA replication, ribosomes, and translation, and a significant decrease in those related to cell differentiation, tissue development, lipid metabolic processes, and peroxisome proliferator-activated receptor signaling. Serum-induced differentiation, but not growth factor-related proliferation, elicits a pronounced lipid accumulation in human meibomian gland epithelial cells. This lipogenic response is unique, and is not duplicated by human conjunctival epithelial cells. CONCLUSIONS. Our results demonstrate that EGF and BPE stimulate human meibomian gland epithelial cells to proliferate. Further, our findings show that action is associated with an upregulation of cell cycle and translation ontologies, and a downregulation of genetic pathways linked to differentiation and lipid biosynthesis.

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