The role of laminins in basement membrane function

Institut für Biochemie II, Medical Faculty, Cologne, Germany.
Journal of Anatomy (Impact Factor: 2.23). 08/1998; 193 ( Pt 1):1-21. DOI: 10.1046/j.1469-7580.1998.19310001.x
Source: PubMed

ABSTRACT Laminins are a family of multifunctional macromolecules, ubiquitous in basement membranes, and represent the most abundant structural noncollagenous glycoproteins of these highly specialised extracellular matrices. Their discovery started with the difficult task of isolating molecules produced by cultivated cells or extracted from tissues. The development of molecular biology techniques has facilitated and accelerated the identification and the characterisation of new laminin variants making it feasible to identify full-length polypeptides which have not been purified. Further, genetically engineered laminin fragments can be generated for studies of their structure-function relationship, permitting the demonstration that laminins are involved in multiple interactions with themselves, with other components of the basal lamina, and with cells. It endows laminins with a central role in the formation, the architecture, and the stability of basement membranes. In addition, laminins may both separate and connect different tissues, i.e. the parenchymal and the interstitial connective tissues. Laminins also provide adjacent cells with a mechanical scaffold and biological information either directly by interacting with cell surface components, or indirectly by trapping growth factors. In doing so they trigger and control cellular functions. Recently, the structural and biological diversity of the laminins has started to be elucidated by gene targeting and by the identification of laminin defects in acquired or inherited human diseases. The consequent phenotypes highlight the pivotal role of laminins in determining heterogeneity in basement membrane functions.

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    ABSTRACT: Objective: Some previous studies have shown important modifications of the basement membrane of psoriatic skin, which could play a key role in alterations of keratinocyte proliferation and differentiation. Changes in distribution of the laminin α1 chain, together with fibronectin, might influence keratinocyte growth, and thus could be responsible for the initiation of psoriasis. In the view of these considerations, we have aimed to determine the expression pattern of laminin and of fibronectin, besides the structural alterations of the epidermis, dermis, and dermoepidermal junction in involved psoriatic skin. Material and methods: Fourteen male psoriasis vulgaris patients and 6 healthy volunteers were studied retrospectively. All psoriatic patients had chronic and stable psoriatic plaque, which had not been treated. Sections were stained with haematoxylin and eosin (H-E), and periodic acid Schiff (PAS) reagent, and were stained immunohistochemically using laminin and fibronectin kits. Results: Histological examination of psoriatic skin showed elongated rete ridges, parakeratosis, epidermal intercellular oedema, exositosis of mononuclear cells into the epidermis, and mononuclear cell inflammation in the dermis. PAS staining revealed the large interruptions of the basement membrane. In psoriatic skin samples, the staining of laminin showed discontinuous, weak, and an uneven disruption in the basement membrane. Staining for fibronectin was pronounced below the basement membrane and showed a reticular or fibrillar pattern in the dermis. Conclusion: The results of our study support the hypothesis that basement membrane alterations together with the alterations in the distribution pattern of laminin and fibronectin may play an important role in the pathogenesis of psoriasis. Psöriatik Deride Histopatolojik Bulgular ve Laminin ve Fibronektin Dağılımı Amaç: Yapılan bazı çalışmalarda psöriatik deride keratinosit proliferasyonu ve farklılaşmasında anahtar rol oynayabilecek bazı önemli bazal membran değişiklikleri olduğu gösterilmiştir. Laminin α1 zinciri ve fibronektin dağılımındaki değişiklikler keratinosit büyümesini etkileyerek psöriasisin başlamasından sorumlu olabilir. Bu görüş doğrultusunda çalışmamızda psöriatik deride dermis, epidermis ve dermo-epidermal bileşkedeki yapısal değişikliklerin yanısıra laminin ve fibronektin dağılım örneğini de incelemeyi amaçladık. Gereç ve Yöntem: Ondört erkek psöriasis vulgaris hastası ve 6 sağlıklı gönüllü retrospektif olarak değerlendirildi. Psöriasisli hastalar kronik ve stabil plakları olan, tedavi almamış hastalardı. Kesitler haematoxylin ve eosin (H-E) ve periodic acid Schiff (PAS) yöntemleri ve laminin ve fibronektin kitleri kullanılarak immunohistokimyasal olarak boyandı. Bulgular: Psöriatik derinin histolojik incelenmesinde rete çıkıntılarında uzama, parakeratoz, epidermal intersellüler ödem, mononükleer hücrelerin epidermise geçişi ve dermiste mononukleer hücre infiltrasyonu saptandı. PAS yöntemiyle bazal membranda geniş kesintiler gözlendi. Psöriatik deride bazal membranda laminin zayıf, kesintili ve düzensiz bir dağılım örneği gösterdi. Fibronektin bazal membran altında belirgindi, dermisde fibriler veya retiküler bir boyanma örneği gösterdi. Sonuç: Çalışmamızın sonuçları psöriasisin patogenezinde bazal membran değişiklikleri ile birlikte laminin ve fibronektin dağılımındaki değişikliklerin önemli rol oynadığı hipotezini desteklemektedir.
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    ABSTRACT: Laminin 5 (α3β3γ2) is specifically present in the basal lamina underneath epithelia with secretory or protective functions, where it is essential for anchoring basal epithelial cells to the underlying extracellular matrix. Laminin 5 is produced by epithelial cells as a 480-kDa precursor that is converted into forms of 440 and 400 kDa. To analyse the processing of laminin 5, we have used monolayer and co-cultures of epithelial cells and fibroblasts. The processing of the 180-kDa laminin α3 chain to 165 kDa in the cell culture medium, and to both 165 and 145 kDa polypeptides in the cell layer, are not modified by the presence of fibroblasts. In contrast, cleavage of the laminin γ2 chain, occurring in the cell culture medium and in the cell layer, is enhanced by the presence of fibroblasts. Further analysis by immunofluorescence staining and laser-scanning microscopy reveals that deposited laminin 5 is present in a fibroblast-associated filamentous meshwork. Only laminin 5 containing a fully processed γ2 chain is present in this fibroblast-associated fraction. These studies show that, although laminin 5 is a product of epithelial cells, fibroblasts contribute to its integration into the extracellular matrix architecture.
    Experimental Cell Research 06/2004; 296(2):223-230. DOI:10.1016/S0014-4827(04)00102-8 · 3.37 Impact Factor
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    ABSTRACT: The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-β peptide (Aβ) in the form of amyloid plaques and neuronal loss. Neural stem cell (NSC) is being scrutinized as a promising cell replacement therapy for various neurodegenerative diseases. However, the unfavorable niche at the site of degenerative disease is hostile to the survival and differentiation of transplanted cells. Here, we undertook in vitro and in vivo works to examine whether a designer self-assemble peptide (DSP), which contains one functional domain Tyr-Ile-Gly-Ser-Arg (YIGSR) derived from laminin, promotes the survival and neuronal differentiation of NSC and behavioral improvement. We found that DSP could undergo spontaneous assembly into well-ordered nanofibers, and it not only facilitated the cell viability in normal culture condition, but also decreased the number of apoptotic cells induced by Aβ in vitro. NSC seeded in DSP showed much more neuronal differentiation than that seeded in self-assemble peptide (SP) or alone. In the AD model, NSC transplantation in DSP-treated AD rats demonstrated much more obvious cognitive rescue with restoration of learning/memory function compared with NSC transplantation in SP, NSC alone, or DSP alone treated ones. Interestingly, DSP enhanced the survival and neuronal differentiation of transplanted NSC. Apoptosis levels in the CA1 region and Aβ level in the hippocampus were significantly decreased in the group of NSC transplantation in DSP. Moreover, synaptic function, indicated by the expression of pre-synaptic protein synapsin-1, was restored and the secretion of anti-inflammatory and neurotrophic factors were increased, such as IL-10, brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulin-like growth factor 1 (IGF-1), while the expression of pro-inflammatory factors were decreased, such as TNF-α and IL-1β. These data firstly unveiled that the biomaterial DSP can maximize the therapeutic benefits of NSC transplantation for AD through improving the survival and differentiation of transplanted stem cells and promoting the effects of neuroprotection, anti-neuroinflammatory and paracrine action. Our results may have important clinical implications for the design of future NSC-based strategies using the biomaterials for various neurodegenerative diseases including AD.
    Molecular Neurobiology 01/2015; DOI:10.1007/s12035-014-9069-y · 5.29 Impact Factor

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