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• W2968894611 abstract "Proteoglycans were first discovered in basement membranes by the presence oftheir sulfate esters and their ability to be detected with cationic dyes (1,2). Thepresence of heparan sulfate proteoglycans in basement membranes was observedby the sensitivity of cationic dye staining to treatment with heparitinase or nitrousacid (3). Since these initial studies, major efforts have concentrated on the isolation and purification of basement membrane proteoglycans. The EngelbrethHolm-Swarm (EHS) tumor, which produces other basement membrane moleculessuch as laminin and collagen IV, was the source used to first isolate a heparansulfate proteoglycan in large quantities which was subsequently called large lowdensity heparan sulfate proteoglycan (4). Antibodies to this proteoglycan showedit was present in all basement membranes including all vascular basement membranes, as well as in many extracellular matrices, and showed the core proteinto be 400 kD (5,6). The antibodies were also used to isolate the first cDNA clones(7) which provided the initial characterization of its core protein. This heparansulfate proteoglycan (HSPG) was then named perlecan, referring to its rotaryshadowed electron microscopy structure which appeared as ‘‘beads along astring’’ (8). Perlecan is one of the most heavily studied proteoglycans, to date.For reviews see Refs. 9-14. This review will concentrate on the recent findings.Since perlecan is found in all basement membranes and many extracellular matrices, it has a wide range of regulatory controls, binding properties, and interactions. Perlecan’s gene structure is enormously complex and the promoter regionhas recently been characterized, thus providing a plethora of information aboutthe regulatory control elements which determine the expression of this proteoglycan. Perlecan is not only regulated by cytokines but can also be bound to them,as well as to growth factors, with high affinity. Some of these interactions involveonly perlecan’s heparan sulfate side chains, and others involve the core protein.Perlecan also appears to be an early response gene since several studies havereported rapid induction of perlecan expression. Perlecan can act as a growthstimulant for some cell types including cancer cells, and is a potent inhibitor ofproliferation for others such as vascular smooth muscle cells. This proteoglycancan act as a coreceptor or prevent other molecules from interacting with theirs. Inaddition, perlecan has now been shown to bind most of the basement membranecomponents as well as several extracellular matrix molecules. Recent studies onthe nematode perlecan gene have provided striking details on the role of perlecanin myofilament formation and organization as well as on how the basement membrane is formed. Perlecan also plays an important role in the development ofpulmonary, intestinal, cartilaginous, muscular, cardiovascular, and organ maturation of mesenchymal tissues. It has recently been shown to have an active rolein the pathogenesis of a wide range of diseases, including Alzheimer’s disease,Scrapie, diabetes, arteriosclerosis, and cancer; and it can be essential to tumorgrowth, involved in the sequestering of cytokines/growth factors, induction ofangiogenesis for tumor blood supply, and in enhancing metastatic potential. Perlecan is even being targeted in the therapies for some of these diseases. Clearly,the ubiquitous expression of this proteoglycan and its potential diversity throughalternative splicing and the attachment of either heparan sulfate or chondroitinsulfate or both types of side chains has led to many recent discoveries and manymore are sure to follow." @default.
• W2968894611 created "2019-08-22" @default.
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• W2968894611 date "2000-04-05" @default.
• W2968894611 modified "2023-09-23" @default.
• W2968894611 title "Heparan Sulfate Proteoglycans in Basement Membranes: Perlecan, Agrin, and Collagen XVIII" @default.
• W2968894611 doi "https://doi.org/10.1201/9780203909720-16" @default.
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