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The Importance of Extracellular Matrix Protein 1 as Basement Membrane Protein in Maintaining Skin Function

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Textbook of Aging Skin

Abstract

The extracellular matrix protein 1 (Ecm1) was identified in 1994 as a novel glycosylated 85-kDa protein secreted in the conditioned medium of the murine osteogenic stromal cell line, MN7 [1]. It was discovered amidst various connective tissue proteins including collagens, osteonectin, and bone sialo protein, and was therefore named Ecm1, although its potential relevance to extracellular matrix physiology was not immediately apparent. The mouse Ecm1 gene has been characterized further by cloning and sequencing of its cDNA, analysis of its expression pattern, and its genomic localization [2]. The 5 kb long Ecm1 gene maps to chromosome 3 and encodes for two distinct splice variants: a complete cDNA clone, Ecm1a, with an open reading frame of 1,677 bp that encodes for a protein of 559 amino acids (aa) (11 exon gene) and a shorter alternatively spliced Ecm1b (lacks exon 8) mRNA of 1.5 kb, coding for a protein of 434 aa [2, 3]. Thereafter, the human ECM1 gene was isolated in 1997 and mapped to chromosome 1q21 [4, 5]. Comparison in the plane structure between the mouse and the human ECM1 gene [4] reveals that the human gene contains one exon less than the mouse gene, that is, the sequence homologous to the sixth and shortest mouse exon [4]. The 5’-upstream regulatory sequences of the mouse Ecm1a gene contains putative binding sites for GATA, Sp1, AP1, and the Ets family of transcription factors. Comparing this region to the equivalent portion of the human gene reveals a strong conservation. The potential AP1 and Sp1 sites are perfectly conserved, while the potential Ets site only differs in one nucleotide between both species, with the human sequence conforming even better to the consensus sequence for this transcription factor family. The Sp1, AP1, and Ets factor-binding regions are necessary for the expression of Ecm1 in the MN7 cell line, while the potential GATA site on the other hand is not conserved between human and murine ECM1 genes and is therefore functionless in the former [3].

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Acknowledgments

We thank Professor Dr. J. Lambert for critically reading this manuscript. The authors would also like to thank all investigators who contributed to ECM1 research and due to word limitations are not cited in the references.

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Sercu, S., Oyama, N., Merregaert, J. (2010). The Importance of Extracellular Matrix Protein 1 as Basement Membrane Protein in Maintaining Skin Function. In: Farage, M.A., Miller, K.W., Maibach, H.I. (eds) Textbook of Aging Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89656-2_8

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  • DOI: https://doi.org/10.1007/978-3-540-89656-2_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-89655-5

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