Importance of Extracellular Matrix Protein 1 (ECM1) in Maintaining the Functional Integrity of the Human Skin

Abstract

Abstract: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 -helices ( 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.

Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction

“…This is the first detection of ECM1 expression in the aging heart. Previous studies have identified an inverse trend in the dermis where ECM1 expression decreases in aging human skin [41, 42]. This opposing finding is likely due to the fact that the aging of human skin is associated with decreased collagen and elastin content in the ECM leading to fragmentation and disorganization of the remaining collagen fibres [42, 43].…”

“…Previous studies have identified an inverse trend in the dermis where ECM1 expression decreases in aging human skin [41, 42]. This opposing finding is likely due to the fact that the aging of human skin is associated with decreased collagen and elastin content in the ECM leading to fragmentation and disorganization of the remaining collagen fibres [42, 43]. In contrast, the aging heart is associated with the accumulation of collagen, elastin and other ECM proteins [38, 40], and a general shift in the expression of various matrix metalloproteinases (MMPs) [44].…”

“…In contrast, the aging heart is associated with the accumulation of collagen, elastin and other ECM proteins [38, 40], and a general shift in the expression of various matrix metalloproteinases (MMPs) [44]. ECM1 has been identified to bind many ECM proteins, and is described as a multifunctional binding core, and a biological glue [25, 33, 42, 45]. Thus, it is likely that ECM1 plays a role in conferring structural stability to the cardiac ECM via its protein-protein binding capacity, particularly in age-associated fibrotic ECM remodelling; similar to the previously proposed role of ECM1 in the skin [42].…”

Prominent corneal nerves: a novel sign of lipoid proteinosis

“…ECM1 is suggested to act as biological glue capable of connecting the basolateral surface of the epidermis to the underlying dermis 23. It has the ability to bind to a number of extracellular matrix molecules, including collagen type IV, fibronectin, hyaluronic acid, chondroitin sulphate, matrix metalloproteases-9 (MMP-9), perlecan, laminin 332, fibulin-1C/D, fibulin-3 and heparin 24.…”

Estudo da expressão do colágeno tipo V e sua relação com a proteína 1 da matriz extracelular no remodelamento da pele de pacientes com líquen escleroso

“…É provável que a diminuição da ECM-1 leve a um aumento da MMP-9 livre (Terlizzi et al, 2004). A MMP-9 livre por sua vez quebra o COL IV gerando fragmentos da cadeia alfa-3 de COL IV conhecido por tumistatina (Sercu et al, 2009). A tumistatina ativa TGF-beta que é conhecido por estimular a proliferação de fibroblastos e induzir a síntese e secreção de proteínas da matriz extracelular (Massague, 1998).…”