TY - JOUR
T1 - Expression and regulation of latent TGF-β binding protein-1 transcripts and their splice variants in human glomerular endothelial cells
AU - Joon, Hyeok Kwak
AU - Ji, Su Woo
AU - Shin, Kunyoo
AU - Hee, Joon Kim
AU - Hoe, Su Jeong
AU - Dong, Cheol Han
AU - Sung, Il Kim
AU - Choon, Sik Park
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
KW - Blood Glucose
KW - Endothelial Cells
KW - Hydrogen Peroxide
KW - Latent TGF-beta binding protein
KW - Splice Variant of LTBP-1
KW - Transforming growth factor beta 1
KW - Vascular Endothelial Growth Factor
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U2 - 10.3346/jkms.2005.20.4.628
DO - 10.3346/jkms.2005.20.4.628
M3 - Article
C2 - 16100456
AN - SCOPUS:24644441412
SN - 1011-8934
VL - 20
SP - 628
EP - 635
JO - Journal of Korean Medical Science
JF - Journal of Korean Medical Science
IS - 4
ER -