Expression and regulation of latent TGF-β binding protein-1 transcripts and their splice variants in human glomerular endothelial cells

Hyeok Kwak Joon, Su Woo Ji, Kunyoo Shin, Joon Kim Hee, Su Jeong Hoe, Cheol Han Dong, Il Kim Sung, Sik Park Choon

Research output: Contribution to journalArticle

Abstract

Latent transforming growth factor (TGF)-β-binding protein (LTBP) is required for the assembly, secretion, matrix association, and activation of latent TGF-β complex. To elucidate the cell specific expression of the genes of LTBP-1 and their splice variants and the factors that regulate the gene expression, we cultured primary human glomerular endothelial cells (HGEC) under different conditions. Basal expression of LTBP-1 mRNA was suppressed in HGEC compared to WI-38 human embryonic lung fibroblasts. High glucose, H 2O2, and TGF-β1 upregulated and vascular endothelial growth factor (VEGF) further downregulated LTBP-1 mRNA in HGEC. RT-PCR with a primer set for LTBP-1S produced many clones but no clone was gained with a primer set for LTBP-1L. Of 12 clones selected randomly, Sca I mapping and DNA sequencing revealed that only one was LTBP-1S and all the others were LTBP-1SΔ53. TGF-β1, but not high glucose, H2O2 or VEGF, tended to increase LTBP-1SΔ53 mRNA. In conclusion, HGEC express LTBP-1 mRNA which is suppressed at basal state but upregulated by high glucose, H2O2, and TGF-β1 and downregulated by VEGF. Major splice variant of LTBP-1 in HGEC was LTBP-1SΔ53. Modification of LTBP-1SΔ53 gene in HGEC may abrogate fibrotic action of TGF-β1 but this requires confirmation.

Original languageEnglish (US)
Pages (from-to)628-635
Number of pages8
JournalJournal of Korean Medical Science
Volume20
Issue number4
StatePublished - Aug 1 2005

Keywords

  • Blood Glucose
  • Endothelial Cells
  • Hydrogen Peroxide
  • Latent TGF-beta binding protein
  • Splice Variant of LTBP-1
  • Transforming growth factor beta 1
  • Vascular Endothelial Growth Factor

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Joon, H. K., Ji, S. W., Shin, K., Hee, J. K., Hoe, S. J., Dong, C. H., Sung, I. K., & Choon, S. P. (2005). Expression and regulation of latent TGF-β binding protein-1 transcripts and their splice variants in human glomerular endothelial cells. Journal of Korean Medical Science, 20(4), 628-635.