Journal of Korean Medical Science

Korean Acad Medical Sciences (대한의학회)
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Expression and Regulation of Latent $TGF-{\beta}$ Binding Protein-1 Transcripts and Their Splice Variants in Human Glomerular Endothelial Cells

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

  • Published : 20050800

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Abstract

Latent transforming growth factor $(TGF)-{\beta}-binding$ protein (LTBP) is required for the assembly, secretion, matrix association, and activation of latent $TGF-{\beta}$ 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, $H_2O_2,\;and\;TGF-{\beta}1$ 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-$1S{\Delta}53.\;TGF-{\beta}1$, but not high glucose, $H_2O_2$ or VEGF, tended to increase $LTBP-1S{\Delta}53$ mRNA. In conclusion, HGEC express LTBP-1 mRNA which is suppressed at basal state but upregulated by high glucose, $H_2O_2,\;and\;TGF-{\beta}1$ and downregulated by VEGF. Major splice variant of LTBP-1 in HGEC was $LTBP-1S{\Delta}53$. Modification of LTBP-$1S{\Delta}53$ gene in HGEC may abrogate fibrotic action of $TGF-{\beta}1$ but this requires confirmation.

Keywords

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