The extracellular matrix of the dermis: flexible structures with dynamic functions

Abstract

The current understanding of the role of extracellular matrix proteins is mainly based on their structural properties and their assembly into complex networks. The multiplicity of interactions between cells, cytokines and growth factors within the networks determines functional units dictating the biophysical properties of tissues. This review focuses on the understanding how alterations in the genes, modifying enzymes or biological functions of extracellular matrix molecules, lead to inborn or acquired skin disorders. Analysis of the disease mechanisms provides the basis for the emerging concept that not solely structural defects of single extracellular matrix proteins are at fault, but rather that the functional unit as a whole is not working properly, causing similar clinical symptoms although the causative genes are entirely different. The understanding of these diseasecausing pathways has already led to surprising new therapeutic developments applied to rare inborn disorders. They now permit to design new concepts for the treatment of more common diseases associated with the accumulation of connective tissue and alterations of the biomechanical properties of the extracellular matrix.

The laminin family

“…Laminin 332 with rudimentary N-terminus and only one copy of the LN domain on the β3 chain provides the core of a unique and biologically important network anchoring the epidermis to the dermis. 76 Although truncated, the N-terminal region of laminin 332 associates with other extracellular components, including at least laminin 311, 77 collagen VII, [78][79][80] collagen XVII 81 and fibulin. 74,82 It is not known whether these interactions are sufficient to maintain anchorage of the N-terminal regions of laminin 332 within the extracellular matrix of the epidermal-dermal basement membrane, or whether additional interactions are required.…”

An Overview of the Beneficial Effects of Hydrolysed Collagen as a Nutraceutical on Skin Properties: Scientific Background and Clinical Studies

“…The main function of this network is to provide structural support to the epidermis. In addition, collagen and elastin together form the extracellular matrix, which gives the skin its structure, elasticity and firmness [10] (Fig. (3)).…”

Effects of Food-Derived Collagen Peptides on the Expression of Keratin and Keratin-Associated Protein Genes in the Mouse Skin

“…Underlying the epidermis is the dermis, which comprises mainly fibroblasts in an extracellular matrix [1]. The current literature indicates that dermal extracellular matrix remodeling is involved in skin homeostasis, aging and wound healing [2], and that dermis-epidermis interactions play an indispensable role in the regulation of these processes [3,4]. Furthermore, the molecular signals exchanged between these compartments also mediate hair follicle formation and hair cycling [5].…”

“…Once secreted into the extracellular space, the amino and carboxyl extensions of procollagen are removed, followed by the alignment of procollagens to generate collagen fibers. These fibers are cross-linked with other components of the extracellular matrix, forming a bioactive network [2]. …”