Basement Membrane Peptides: Functional Considerations and Biomedical Applications in Autoimmunity

Abstract

Basement membranes are specialized extracellular matrices that surround certain cell types (muscle cells, adipose cells, etc) and are present under the basal surface of cells exhibiting polarity (epithelial, endothelial and mesothelial cells). They have a unique macromolecular composition, consisting mainly of type IV collagen isoforms, laminin isoforms, entactin/nidogen, and perlecan. These components self associate and interact with each other to form networks. Other macromolecules may be found in specialized basement membranes. In this short review, the role of selected basement membrane proteins in autoimmune diseases will be highlighted. As an example, Goodpasture's syndrome will be presented and the relatively long quest for identification of the antigenic epitope on specific domains of the alpha3(IV)NC1 will be summarized. Chagas disease will be discussed as an example of laminin-mediated autoimmunity, with emphasis on the role of sugar-based antigenic epitope(s) will be presented. Immune-mediated tubulointerstitial nephritis will be introduced and the role of a synthetic peptide in detecting proximal tubule damage in acute renal failure will be discussed. Auto-immune diseases where other basement membrane macromolecules are involved will be mentioned. Finally, the importance of understanding the functions served by domains at close proximity to the antigenic epitope(s) will be highlighted.

Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction

“…The supramolecular structure of Col IV was extensively studied during the last two decades (Timpl and Brown, 1996;Gelse et al, 2003;White et al, 2004;Charonis et al, 2005;Brown et al, 2006;LeBleu et al, 2007;Khoshnoodi et al, 2008). Once secreted, the triple-helical heterotrimeric molecules of Col IV self-associate to form a 2D network which serves as molecular scaffold for other BM components, such as laminin, perlecans and proteoglycans (Timpl and Brown, 1996;Brown et al, 2006).…”

“…Once secreted, the triple-helical heterotrimeric molecules of Col IV self-associate to form a 2D network which serves as molecular scaffold for other BM components, such as laminin, perlecans and proteoglycans (Timpl and Brown, 1996;Brown et al, 2006). Detailed in situ analysis of high resolution electron micrographs revealed that Col IV molecules self-assemble in the BM forming polygonal networks held together by overlapping and lateral interactions along the triple-helical domain and the N-and C-terminal end-domains ( Timpl and Brown, 1996;Charonis et al, 2005).…”

“…Despite the extensive research on the biochemistry and physiology of Col IV Gelse et al, 2003;Keresztes et al, 2006) and its involvement in a number of human disorders (Gelse et al, 2003;Charonis et al, 2005), surprisingly little is known about the behavior of Col IV at the biomaterials interface, which in turn, determines the successful cellular interaction.…”

“…In this study we were particularly interested in the behavior of adsorbed type IV collagen (Col IV) -a unique multifunctional matrix protein that plays a crucial role in the organization of the basement membrane (BM). The BM is a highly specialized ECM common to many types of tissues providing spatial organization to the cells and involved in a remarkable number of physiological and pathological processes, such as cell adhesion, migration, development, wound healing and cancer progression (Timpl and Brown, 1996;Charonis et al, 2005;Brown et al, 2006;LeBleu et al, 2007;Khoshnoodi et al, 2008); in addition, it serves as a reservoir for growth factors and enzymes and is responsible for the molecular sieving (Timpl and Brown, 1996). The BM is a fine (approximately 100-300 nm thick) structure that may be considered as two dimensional (2D) in respect to the range of cell size.…”

Laminin-332-Integrin Interaction: A Target For Cancer Therapy?

“…These include various collagens, elastin, fibronectin, laminin, fibulin, perlecan, entactin, and nidogen [7]. Among these, laminin is a glycoprotein produced mainly by epithelial cells and endothelial cells.…”