Expression of hyaluronan synthase in intraocular proliferative diseases: regulation of expression in human vascular endothelial cells by transforming growth factor-beta

Jpn J Ophthalmol. Nov-Dec 2003;47(6):557-64. doi: 10.1016/j.jjo.2003.09.001.


Purpose: To investigate the role of hyaluronan (HA) and elucidate the mechanisms that regulate the expression of hyaluronan-synthesizing enzymes in vascular endothelial cells (VECs) in intraocular proliferative diseases.

Methods: Cultured VECs were used. Hyaluronan synthase (HAS) expression was determined on the mRNA products obtained by reverse transcription polymerase chain reaction (RT-PCR). The effect of transforming growth factor-beta(1)(TGF-beta(1)) and/or platelet-derived growth factor-BB (PDGF-BB) on HAS expression was examined by quantitative RT-PCR and Western blot analysis. HAS expression in intraocular proliferative membranes was observed by immunohistochemistry.

Results: Cultured VECs expressed the three HAS isoforms. Stimulation of VECs with TGF-beta(1) induced a marked increase in the expression level of HAS2 mRNA and protein. The stimulatory effect of PDGF-BB was less potent. A synergistic or additive effect between TGF-beta(1) and PDGF-BB-induced HA synthesis was not observed. Furthermore, HAS1 and HAS2 exhibited differential expression in VECs and non-VECs populating intraocular proliferative membranes.

Conclusions: The expression of each HAS isoform is regulated differently by growth factors and cytokines in VECs. Importantly, HA-synthesizing enzymes were expressed in cells populating proliferative membranes obtained from eyes of patients with proliferative vitreoretinal diseases, and thus may be key molecules in the events that control progression of the proliferative diseases.

MeSH terms

  • Becaplermin
  • Cells, Cultured
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / pathology
  • Eye Diseases / enzymology*
  • Eye Diseases / pathology*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Glycosyltransferases*
  • Humans
  • Hyaluronan Synthases
  • Immunohistochemistry
  • Membrane Proteins*
  • Membranes / enzymology
  • Membranes / pathology
  • Platelet-Derived Growth Factor / pharmacology
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Transferases*
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1
  • Xenopus Proteins*


  • Membrane Proteins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • Recombinant Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Xenopus Proteins
  • Becaplermin
  • Transferases
  • Glycosyltransferases
  • Glucuronosyltransferase
  • HAS1 protein, Xenopus
  • HAS2 protein, human
  • HAS3 protein, human
  • Has2 protein, Xenopus
  • Hyaluronan Synthases