Basement membranes in skin: unique matrix structures with diverse functions?
- 940 Downloads
The view of extracellular matrix (ECM) has evolved from a merely scaffolding and space filling tissue element to an interface actively controlling cellular activities and tissue functions. A highly specialized form of ECM is the basement membrane (BM), an ubiquitous sheet-like polymeric structure composed of a set of distinct glycoproteins and proteoglycans. In this review we are largely focusing on function and assembly of BM in skin (1) at the dermo-epidermal interface and (2) in the resident micro-vasculature. The role of the non-polymeric components perlecan and particularly nidogen is exemplified by reviewing experiments based on genetic approaches and adequate experimental skin models in vivo and in vitro. While in mice total deficiency of one of these components is eventually developmentally lethal, the severity of the defects varies drastically between tissues and also the skin models recapitulating BM formation in vitro. There is accumulating evidence that this relies on the mechanical properties, the molecular composition of the BM, the adjacent ECM or connective tissue, the dynamics of molecular assembly, and ‘minor’ tissue-specific modifier or adapter components. Though the role of nidogen or perlecan is still remaining a controversial issue, the statements ‘being essential for BM/or not’ should be consequently referred to the developmental, tissue, and functional (e.g., repair) context.
KeywordsDermo-epidermal junction Basement membrane Molecular composition Molecular assembly Nidogen function Organotypic co-culture Micro-vasculature Ultrastructure
The work was in part supported by the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich (SFB) 589 at the University of Cologne, the grants NI-304/11-1 (Roswitha Nischt), BR-530/8-1 (Dirk Breitkreutz), and industrial grants (Sanofi-Aventis); furthermore we like to thank all students and colleagues involved or contributing to these studies at any stage, also by many fruitful discussions. We apologize to the many scientists whose paper we were unable to cite owing to space constraints.
- Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005) A simplified laminin nomenclature. Matrix Biol 24:326–332PubMedCrossRefGoogle Scholar
- Limat A, Stockhammer E, Breitkreutz D, Schaffner T, Egelrud T, Salomon D, Fusenig NE, Braathen LR, Hunziker T (1996) Endogenously regulated site-specific differentiation of human palmar skin keratinocytes in organotypic cocultures and in nude mouse transplants. Eur J Cell Biol 69:245–258PubMedGoogle Scholar
- Mirancea N, Schmidt C, Daum N, Tomakidi P, Stark HJ, Fusenig NE, Breitkreutz D (2002) Basement membrane defects in xeno-grafts of malignant human cells. In: Witz IP (ed) Proceedings of the 2nd international conference tumor microenvironment. Monduzzi, Bologna, pp 55–58Google Scholar
- Müller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 42:735–744Google Scholar
- Sher I, Zisman-Rozen S, Eliahu L, Whitelock JM, Maas-Szabowski N, Yamada Y, Breitkreutz D, Fusenig NE, Arikawa-Hirasawa E, Iozzo RV, Bergman R, Ron D (2006) Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermis formation. J Biol Chem 281:5178–5187PubMedCrossRefGoogle Scholar
- Stark HJ, Willhauck MJ, Mirancea N, Boehnke K, Nord I, Breitkreutz D, Pavesio A, Boukamp P, Fusenig NE (2004) Authentic fibroblast matrix in dermal equivalents normalizes epidermal histogenesis and dermo-epidermal junction in organotypic co-culture. Eur J Cell Biol 83:631–645PubMedCrossRefGoogle Scholar