Extracellular Matrix Protein 1 (ECM1) Is Decreased By Chronological Aging and Increased Upon UV Exposure

Extracellular matrix protein 1 (ECM1) is an extracellular matrix glycoprotein containing motifs with cysteine pattern as the binding sites with other matrix protein or molecules in skin. ECM1 consists of four binding domains for interacting with different ECM molecules ECM1 binds various skin structural and ECM molecules such as perlecan, laminin 332, fibulin-1C/D, fibulin-3 and heparin, as well as dermal interstitial molecules MMP-9, collagen type IV, fibronectin, hyaluronic acid and chondroitin sulphate. ECM1 is one of the proteins connecting the basal layer of epidermis to the basement membrane (BM) and BM to the dermis. ECM1 functions as the “biological glue” in maintaining dermal- epidermal skin structure, skin’s biological function, physiology and homeostasis. Genetic skin diseases suggest a pivotal biological function of ECM1 in human skin – loss of function mutations in the ECM1 gene causes the rare genetic skin disease – the autosomal recessive genodermatosis lipoid proteinosis and the autoimmune disease lichen sclerosus with the presence of ECM1 autoantibody. Similar skin pathologies are observed in both diseases.

ECM1 may be involved in epidermal differentiation because ECM1 gene maps to a region on chromosome where a gene cluster generally known as the “epidermal differentiation complex” is located, containing a remarkable density of genes that fulfill important functions in epidermal differentiation. ECM1a was found in the epidermal basal layer, in dermal blood vessels, the outer root sheath of hair follicles and in sebaceous lobules and epithelium of sweat glands, while ECM1b was expressed in the suprabasal layers of the epidermis. ECM1 binds and interacts with perlecan, an important intrinsic molecule in skin organogenesis. However, in vitro and in vivo experiments revealed no indispensable role for ECM1 in the terminal differentiation process of epidermal keratinocytes. ECM1 is dispensable for terminal differentiation of keratinocytes in unstressed conditions. However, it remains possible that upon stress stimulation, ECM1 may be necessary and essential for the maintenance of epidermal differentiation and homeostasis. Another indication for a possible regulatory role of ECM1b is the presence of two N-glycosylation sites which may bind to epidermal cell surface receptors and may activate certain signal transduction pathways.

ECM1 also plays an important role in the maintenance of the dermal-epidermal communication. ECM1a/c was also found in the network of matrix suprastructures of the basement membrane which is primarily compose of ECM proteins laminin 332 and collagen type IV. The role of ECM1 as a “biological glue” of dermal-epidermal junction structure is base on the fact that ECM1 can bind to most of the important ECM molecules of the basement membrane zone such as perlecan, fibulin-1C-and D, matrix metalloproteinase (MMP)-9 , laminin 332, fibulin-3, collagen type IV, heparin, hyaluronic acid and chondroitin sulphate A. In addition, it also enhances the binding between laminin 332 and collagen IV.

ECM1 is suggested to play a role in skin adhesion, differentiation, scarring, angiogenesis and basement membrane integrity, all of which are important processes in the intrinsic (chronological) as well as the extrinsic (photo) ageing process. ECM1 is one of the many ECM proteins that are significantly decreased in intrinsically aged skin without chronic UV exposure. The decreased ECM1 expression in chronologically aged skin may have profound effects on dermal and epidermal homeostasis, leading to the clinical features of atrophy in both of the skin layers.

Extracellular matrix protein 1 (ECM1) in human skin is decreased by age and increased upon ultraviolet exposure. There are evidence for the involvement of ECM1 in photoaging. A photoprotective role of ECM1 in
skin is proposed based on the research findings. ECM1 was increased in both lower and upper layers of epidermis, induced by chronically UV-exposure, when compared to UV protected skin. UV-irradiation induces fibroblasts to produce more matrix metalloproteinases MMP-1, MMP-3 and MMP-9; MMP-3 degrades many ECM1 binding molecules such as collagen IV, laminin 332, fibronectin and proteoglycans (perlecan). However, the exact mechanism for the proposed photoprotective role of ECM1 is not yet known.

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