This study reviewed some new aspects of the modular proteoglycan perlecan, a colossal proteoglycan with a 467 kDa core protein and five distinct functional domains. Perlecan is a heparan sulphate proteoglycan that transiently displays native CS sulphation motifs 4-C-3 and 7-D-4 during tissue morphogenesis these are expressed by progenitor cell populations during tissue development. Perlecan is susceptible to fragmentation by proteases during tissue development and in pathological tissues particularly in domains IV and V. The fragmentation pattern of domain IV has been suggested as a means of grading prostate cancer. Domain V of perlecan is of interest due to its interactive properties with integrin α5β1 that promotes pericyte migration enhancing PDGF-BB-induced phosphorylation of PDGFRβ, Src homology region 2 domain-containing phosphatase-2, and focal adhesion kinase supporting the repair of the blood brain barrier following ischaemic stroke. Fragments of domain V can also interact with α2β1 integrin disrupting tube formation by endothelial cells. LG1-LG2, LG3 fragments can antagonise VEGFR2, and α2β1 integrin interactions preventing angiogenesis by endothelial cells. These domain V fragments are of interest as potential anti-tumour agents. Perlecan attached to the luminal surfaces of endothelial cells in blood vessels acts as a flow sensor that signals back to endothelial and smooth muscle cells to regulate vascular tone and blood pressure. Perlecan also acts as a flow sensor in the lacuno-canalicular space regulating osteocytes and bone homeostasis. Along with its biomechanical regulatory properties in cartilaginous tissues this further extends the functional repertoire of this amazingly diverse functional proteoglycan.

这项研究回顾了模块化蛋白聚糖 perlecan 的一些新方面，这是一种具有 467 kDa 核心蛋白和五个不同功能域的巨大蛋白聚糖。Perlecan 是一种硫酸乙酰肝素蛋白多糖，在组织形态发生过程中瞬时显示天然 CS 硫酸化基序 4-C-3 和 7-D-4，这些基序在组织发育过程中由祖细胞群表达。Perlecan 在组织发育过程中和在病理组织中，特别是在结构域 IV 和 V 中易受蛋白酶的破坏。结构域 IV 的片段化模式已被建议作为前列腺癌分级的一种手段。Perlecan 的结构域 V 是令人感兴趣的，因为它与整合素 α5β1 的相互作用特性促进周细胞迁移，增强了 PDGF-BB 诱导的 PDGFRβ 磷酸化，Src 同源区 2 域含磷酸酶-2，和粘着斑激酶支持缺血性中风后血脑屏障的修复。结构域 V 的片段还可以与 α2β1 整合素相互作用，破坏内皮细胞的管形成。LG1-LG2、LG3 片段可以拮抗 VEGFR2 和 α2β1 整合素相互作用，从而阻止内皮细胞的血管生成。这些域 V 片段作为潜在的抗肿瘤剂是令人感兴趣的。附着在血管内皮细胞腔表面的 Perlecan 作为流量传感器，向内皮细胞和平滑肌细胞发送信号，以调节血管张力和血压。Perlecan 还充当腔隙小管空间中的流量传感器，调节骨细胞和骨稳态。