Basement membranes and human disease

Abstract

Abbreviations BM: basement membrane, NMJ neuromuscular junction, DEJ dermo epidermal junction, SJS Schwartz Jampel syndrome, DDSH Dyssegmental dysplasia silverman handmaker type, EB epidermolysis bullosa, GBM glomerular basement membrane 1 AbstractIn 1990 the role of basement membranes in human disease was established by the identification of COL4A5 mutations in Alport's syndrome. Since then the number of diseases caused by mutations in basement membrane components has steadily increased as has our understanding of the roles of basement membranes in organ development and function. However, many questions remain as to the molecular and cellular consequences of these mutations and how they lead to the observed disease phenotypes. Despite this, exciting progress has recently been made with potential treatment options for some of these so far incurable diseases.

Collagen VII plays a dual role in wound healing

“…It is synthesized and secreted by both epidermal keratinocytes and dermal fibroblasts and undergoes a multistep process of proteolytic maturation and supramolecular assembly to form anchoring fibrils, which secure strong attachment of the epidermis to the underlying dermis (14). Abnormalities of the anchoring fibrils are associated with dystrophic EB, a form of skin fragility in which blisters and wounds heal with scarring (15)(16)(17).…”

Dynamic Interactions of Epidermal Collagen XVII with the Extracellular Matrix

“…7 HDs play an important role in cell attachment to the epidermal basement membrane, as shown indirectly by abnormalities of HDs in congenital and acquired blistering diseases, such as junctional epidermolysis bullosa and pemphigoid diseases. 8,9 In addition to integrin ␣6␤4 and laminin 332, HDs contain BP230 and plectin as intracellular components and CD151 and collagen XVII as transmembrane components. 7 Elucidation of biologic consequences of mutations in the genes encoding for these proteins has uncovered both laminin 332 and collagen XVII as vital players in cell-ECM interactions.…”

Bone and Cartilage from Stem Cells: Growth Optimalization and Stabilization of Cell Phenotypes

“…Furthermore, the mir-29 family (MIR-29a,b,c) of microRNAs was down-regulated, and putative target transcripts of genes like COL1A1, COL4A1, COL4A5, COL5A1, COL21A1, BMP1, ID1, TNFAIP6, and FBN1 should be upregulated. According to their alleged function, the interaction of the 29-family of microRNAs is expected when the collagens are concerned (Eyre 2002;Almarza and Athanasiou 2004;Goldring, Tsuchimochi et al 2006;Davies, Chang et al 2007;Shahdadfar, Loken et al 2008;Heinegard 2009;Van Agtmael and Bruckner-Tuderman 2010), but does not comply with the expected down-regulation of BMP1, ID1, and TNFAIP6. Cumulative compatibility score is now down to 73%.…”