A current view of perlecan in physiology and pathology: A mosaic of functions

Abstract

Perlecan, a large basement membrane heparan sulfate proteoglycan, is expressed in a wide array of tissues where it regulates diverse cellular processes including bone formation, inflammation, cardiac development, and angiogenesis. Here we provide a contemporary review germane to the biology of perlecan encompassing its genetic regulation as well as an analysis of its modular protein structure as it pertains to function. As perlecan signaling from the extracellular matrix converges on master regulators of autophagy, including AMPK and mTOR, via a specific interaction with vascular endothelial growth factor receptor 2, we specifically focus on the mechanism of action of perlecan in autophagy and angiogenesis and contrast the role of endorepellin, the C-terminal fragment of perlecan, in these cellular and morphogenic events.

Injury and defective regeneration of the epithelial basement membrane in corneal fibrosis: A paradigm for fibrosis in other organs?

“…BMs are highly specialized extracellular matrices assembled primarily from laminins, collagens, heparin sulfate proteoglycans, and nidogens, although the precise composition is tissue-specific [27-29]. They are frequently recognized at the transmission electron microscope (TEM) level as two adjacent layers termed the lamina lucida and lamina densa (Fig.…”

“…Once initiated, the laminin scaffold enables recruitment and assembly of remaining BM components, including nidogen-1, nidogen-2, perlecan, and collagen type IV, to regenerate the structurally and functionally mature BM [27-29]. …”

Proteoglycans in normal physiology and carcinogenesis

“…Перлекан (ГСПГ 2) (perlecan/HSPG2) является ос-новным компонентом базальных мембран, наряду с ламинином, коллагеном 4 и нидогеном/энтактином [36]. Он экспрессируется в широком спектре тканей, где регулирует разнообразные клеточные процессы, включая формирование костей, воспаление и ангио-генез, в первую очередь благодаря его способности взаимодействовать с различными лигандами и рецеп-торами тирозинкиназ.…”

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

“…Their properties strongly depend on their composition in terms of, both, collagens and non-collagenous molecules (e.g. COMP, matrilins, decorin, fibromodulin, lumican, perlecan, and collagen VI-containing microfibrils) [8][9][10][11][12][13]. In cartilage fibrils, for example, the inclusion of collagen XI as a fibrillar nucleus is vital for the incorporation of the main component, collagen II [14,15].…”