Importance of Extracellular Matrix Protein 1 (ECM1) in Maintaining the Functional Integrity of the Human Skin
Sandy Sercu1, 2, Noritaka Oyama3, Joseph Merregaert*, 1
Identifiers and Pagination:Year: 2009
First Page: 44
Last Page: 51
Publisher Id: TODJ-3-44
Article History:Received Date: 08/10/2008
Revision Received Date: 27/10/2008
Acceptance Date: 29/10/2008
Electronic publication date: 20/3/2009
Collection year: 2009
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The extracellular matrix protein 1 (ECM1) is an 85 kDa glycoprotein first identified in 1994. The threedimensional structure of ECM1 based on the third serum albumin domain was determined by in silico modelling in order to predict the most important binding site(s) of ECM1 with other protein partners in human skin. ECM1 consists of four domains: a first domain existing of α -helices (α D1), the serum albumin subdomain-like (SASDL) domain 2, the sequence homology comparable with the first subdomain of the third serum albumin domain, SASDL3 and SASDL4, resulting in four “finger-like” structures ideal for binding with different proteins. A role for ECM1 was proposed in endochondral bone formation, angiogenesis and skin differentiation. Increased evidence has emerged for a pivotal biological function of ECM1 in human skin; loss of function mutations in the ECM1 gene causes the autosomal recessive genodermatosis lipoid proteinosis and auto-antibodies against ECM1 in the auto-immune disease lichen sclerosus, sharing comparable skin pathology in the affected lesions. ECM1 is capable of binding variable skin structural and extracellular matrix molecules like perlecan, laminin 332, fibulin-1C/D, fibulin-3 and heparin, as well as dermal interstitial molecules like MMP-9, collagen type IV, fibronectin, hyaluronic acid and chondroitin sulphate. In this way, ECM1 could be one of the proteins capable of connecting the basolateral surface of the epidermis through the basement membrane to the underlying dermis, which suggest a role for ECM1 as "biological glue" in maintaining skin integrity and function.