Abstract
Treatment of mesangial cells with either phorbol 12-myristate 13-acetate (PMA) or interleukin-1beta induces an increase in laminin B2 chain mRNA levels. In other systems, activation of gene expression by these agents is transcriptionally mediated. To identify transcription factors that control expression of laminin B2 chain gene, we employed a strategy consisting of a computer-based analysis of murine and human gene promoter sequences and gel shift assays. Although overall the laminin B2 chain promoters from the two species have low sequence similarity, the mouse promoter contained sequences that were also contained in one motif, 5'-CCCCGCCCACCTCGCGCGC-3', designated bcn-1, from the human promoter. Treatment of mesangial cells with either PMA or interleukin-1beta induced a transient increase in nuclear DNA binding activity, designated BCN-1, recognized the bcn-1 motif in a gel shift assay. A single nucleotide replacement in the bcn-1 motif abolished DNA binding, indicating that bcn-1.BCN-1 complex formation is highly specific. In transient transfections, the ability of PMA to induce the laminin B2 chain promoter was abolished by mutating the bcn-1 motif. These results suggest that the bcn-1 element and its cognate inducible BCN-1 protein regulate laminin B2 chain gene transcription.
Highlights
These results suggest that the bcn-1 element and its along with NF-B and Sp1 might play a role in the transcripcognate inducible BCN-1 protein regulate laminin B2 tional control of expression of laminin genes
Northern Blot Analysis of the Laminin B2 Chain mRNA Levels in Mesangial Cells Treated with Cytokines—In the glomerulus, laminin is a major constituent of the lamina rara externa of the glomerular basement membrane [13]
To elucidate the potential mechanisms that are responsible for the regulation of laminin production in glomerular cells, we examined the expression of laminin B2 chain mRNA levels in response to treatment of mesangial cells with a number of known cytokines and mitogens
Summary
These results suggest that the bcn-1 element and its along with NF-B and Sp1 might play a role in the transcripcognate inducible BCN-1 protein regulate laminin B2 tional control of expression of laminin genes. Insight into the transcriptional regulation of laminin genes, we used a computer-based analysis to compared the sequences of the murine and the human laminin B2 chain gene promoters. We demonstrate that in mesangial cells IL-1-, membrane [1] It is a large non-collagenous glycoprotein com- PMA-, and TGF-- induced transient increase in laminin B2 posed of three chains connected by an ␣-helical coiled-coil do- chain mRNA levels is preceded by the induction of nuclear main [2]. The basement membrane contains only a unique set of hancer element, designated bcn-1, contained within both the laminin chain heterotrimers; they all contain B2 chain in a rodent and the human laminin B2 chain gene promoter. The level and distribution of laminin in the glomerular basement membrane varies with types of glomerular disease [11, 12].
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