PubMed · 7702272
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Y Sarret, J F Nicolas, P Verrando, D Schmitt. 1994. [Dermo-epidermal junction: current update].. https://pubmed.ncbi.nlm.nih.gov/7702272/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
During progression from benign nevus to vertical growth phase melanoma, melanocytes acquire the ability to invade into the dermis. This process requires rupture of the basal lamina and dissolution of dermal type I collagen. Metastases-derived human melanoma MIM cells have an invasive ability in vitro which is dependent on metalloproteinases. In the present study we analysed the role of type I collagenase (MMP-1) in melanoma invasion using MIM cells in which the constitutive expression of MMP-1 was suppressed by stable transfection with a plasmid vector expressing a 777 bp antisense fragment of MMP-1 genomic DNA. Two clones were isolated in which MMP-1 mRNA expression was blocked by 90-96% with a corresponding loss in protein synthesis. In their morphological appearance and growth rate in vitro these cells were indistinguishable from wild type cells or control cells transfected with the same vector expressing the MMP-1 fragment in the sense orientation. Their mRNA and protein levels for type IV collagenase (MMP-2) were unchanged as assessed by Northern and Western blot analyses and by gelatin zymography. However, when the invasive ability of the cells was measured, we found that in addition to type I collagen, invasion through type IV collagen and a reconstituted, type IV collagen-containing basement membrane (Matrigel) were also significantly inhibited as compared to normal or sense-transfected cells. The results indicate that despite the presence of functional MMP-2, degradation of type IV collagen matrices by the melanoma cells was dependent on expression of MMP-1.
Normal glomerular capillaries filter plasma through a basement membrane (GBM) rich in alpha3(IV), alpha4(IV), and alpha5(IV) chains of type IV collagen. We now show that these latter isoforms are absent biochemically from the glomeruli in patients with X-linked Alport syndrome (XAS). Their GBM instead retain a fetal distribution of alpha1(IV) and alpha2(IV) isoforms because they fail to developmentally switch their alpha-chain use. The anomalous persistence of these fetal isoforms of type IV collagen in the GBM in XAS also confers an unexpected increase in susceptibility to proteolytic attack by collagenases and cathepsins. The incorporation of cysteine-rich alpha3(IV), alpha4(IV), and alpha5(IV) chains into specialized basement membranes like the GBM may have normally evolved to protectively enhance their resistance to proteolytic degradation at the site of glomerular filtration. The relative absence of these potentially protective collagen IV isoforms in GBM from XAS may explain the progressive basement membrane splitting and increased damage as these kidneys deteriorate.
Age-related maculopathy (ARM) is a degenerative disorder of the central part of the retina with a rising prevalence in patients 50 years of age and older, and comprises different histopathological changes. The morphologic changes in ARM are described and illustrated with light-microscopical, electron microscopical, and fundus pictures. Furthermore, the most important biochemical data are given. The most prominent aging changes in early stages of ARM are drusen and basal laminar deposit (BLD), both extracellular deposits, that are assumed to be important in the development of ARM. Drusen accumulate within Bruch's membrane, whereas BLD is present between Bruch's membrane and the retinal pigment epithelium. Although the histopathologic characteristics of the deposits are well documented, the chemical composition has only been partly resolved. Biochemical analysis of these deposits is necessary to determine the source of the deposits and to find possible ways to avoid or treat them. The late stages of ARM, geographic atrophy, and neovascular (disciform) degeneration, are called age-related macular degeneration (AMD), and result in severe and irreversible visual impairment. Since there is still no adequate therapy for the majority of people disabled by AMD, and because of the aging population resulting in even more patients with this disease, it is necessary to intensify the research on ARM in order to prevent AMD or find a therapy for it.