Perlecan (basement membrane heparan sulfate proteoglycan) and its role in oral malignancies: An overview.

Perlecan means pearl-like structures. Perlecan is a large proteoglycan (400-500 kDa) present in virtually all vascularized tissues with a distribution that is primarily confined to basement membranes including those of oral mucosa. It is a basement membrane-type heparan sulfate proteoglycan. Perlecan is synthesized by basal cells and fibroblasts adjacent to the basal lamina . Perlecan is also synthesized by vascular endothelial and smooth muscle cells present in the extracellular matrix. It has been demonstrated in recent years that perlecan is distributed in the stromal space of various pathophysiological conditions. The complex pleiotropy of perlecan suggests that this gene product is involved in several developmental processes, at both early and late stages of embryogenesis, as well as in cancer and diabetes. In the oral cavity, perlecan expression is reported to basal cells in normal mucosa and its expression increases in precancer and cancerous conditions. It is also expressed in various odontogenic tumors such as ameloblastoma, keratocyst odontogenic tumor, and also salivary gland tumors such as adenoid cystic carcinoma, mucoepidermoid carcinoma, etc.

SHh activity and localization is regulated by perlecan

Proliferation and cell fate determination in the developing embryo are extrinsically regulated by multiple interactions among diverse secreted factors, such as Sonic Hedgehog (SHh), which act in a concentration-dependent manner. The fact that SHh is secreted as a lipid-modified protein suggests the existence of a mechanism to regulate its movement across embryonic fields. We have previously shown that heparan sulfate proteoglycans (HSPGs) are required for SHh binding and signalling. However, it was not determined which specific HSPG was responsible for these functions. Here we evaluated the contribution of perlecan on SHh localization and activity. To understand the mechanism of action of perlecan at the cellular level, we studied the role of perlecan-SHh interaction in SHh activity using both cell culture and biochemical assays. Our findings show that perlecan is a crucial anchor and modulator of SHh activity acting as an extracellular positive regulator of SHh.

Expression of heranase and perlecan in the retina of mouse with oxygen-induced retinopathy / 眼科研究

Background Heparanase degrade heparan sulfate side chains of heparan sulfate proteoglycans in the extracellular matrix.Heparanase induces angiogenesis and likely promotes the vascularization of tumor.ObjectiveThe present study is to investigate the expression of heparanase and perlecan in retinas with oxygen-induced retinopathy.Methods Sixty-five clean neonatal C57BL/6J mice were raised in a hyperbaric oxygen box with a volume percentage of 75%±2% for 5 days and then returned to the normal air room.Another 65 matched mice were raised in the normal environment as controls.Evans blue was infused by the superior vena cava in all the mice on postnatal days 12,13,17,21 and 30,afterwards fluorescein angiography was performed and then the mice were sacrificed.The retinas of mice were isolated and prepared and the retinal vessels were examined under a fluorescent microscope and optical microscope.Heranase and perlecan mRNA was detected using reverse transcription PCR (RT-PCR).Heranase and perlecan proteins were detected by Western blot.The analysis of variance was used to compare the mRNA and the protein levels of heranase and perlecan between the experimental and control groups.Results The expression of heparanase mRNA in the retinas of different ages of mice and the different groups showed significant differences (F_(group)=16.303,P=0.000;F_(time)=18.614,P=0.000;F_(interaction)=11.299,P=0.000),and the expression of heparanase mRNA was significantly enhanced in mice from postnatal days 12,13,17 and 21 compared with normal control mice (P=0.001,0.000,0.000,0.001,respectively).The expression of heparanase protein in the retinas of different ages of mice and the different groups followed the same tendency(F_(group)=458.134,P=0.000;F_(time)=78.466,P=0.000;F_(interaction)=71.398,P=0.000).The expression of perlecan mRNA in the retinas of different ages of mice and the different groups showed significant differences (F_(group)=7.351,P=0.013;F_(time)=9.098,P=0.000;F_(interaction)=3.349,P=0.000),and increase in differences also were clearly seen in mice from postnatal days 13,17 and 21 compared with normal control mice (P=0.048,0.000,0.003,respectively).Conclusion The expression of heparanase and perlecan is associated with the development and progression of retinal neovascularization,and perlecan and heparanase together produce a synergistic effect.Heparanase and perlecan may participate in the angiogenesis of oxygen-induced retinopathy.

An Immuno -Electron Microscopic Study for Perlecan in the Synovium of Degenerative Arthritis of Knee / 대한해부학회지

This study was designed to observe the expression of perlecan in the normal and degenerative arthritic synovial membrane. By using the immunohistochemical staining and immuno -electron microscopical gold labeling techniques, we observed five materials of normal and degenerative arthritic synovia each. The results were as follows. 1. By the immunohistochemical methods, perlecan -positive staining was seen on the 1 ~2 cell layers of the normal synovial membrane. But, a weaker staining compared to that seen in the normal synovial membrane was found in the degenerative arthritic synovial membrane. 2. Under the electron microscopic observation, perlecan was largely distributed in the rough endoplasmic reticulum of the secretory synovial cell, and in the vacuoles of the phagocytic synovial cell on the normal synovium of the human knee joint. It was also found in the extracellular matrix of the synovial membrane. 3. Perlecan -positive cells were also identified on the degenerative arthritic synovium of the human knee joint. However, fewer perlecan was observed here than that found in the normal synovium. In conclusion, perlecan is synthesized by the secretory synovial cells and degraded by the phagocytic synovial cells. And it, known as a major component of the basement membrane, also proven to exist in the extracellular matrix of the synovial membrane having no basement membrane. From the fact that less perlecan was observed in the degenerative arthritis, perlecan is might to play a major role in the degenerative process.