title: Effect of growth factors on the proliferation and gene expression of human meibomian gland epithelial cells.
abstract: OBJECTIVE
  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 + 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.
authors.affiliation: Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Liu
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kam
authors.forename: Juan
authors.initials: J
authors.lastname: Ding
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hatton
authors.forename: David A
authors.initials: DA
authors.lastname: Sullivan
mesh_terms: D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D050356:Lipid Metabolism; D008537:Meibomian Glands / Q000166:cytology*; D010902:Pituitary Gland / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014020:Tissue Extracts / Q000494:pharmacology*
chemical_list: D014020:Tissue Extracts; D004815:Epidermal Growth Factor