Basement membrane

The basement membrane is a thin, fibrous, extracellular matrix of tissue that separates the lining of an internal or external body surface from underlying connective tissue in metazoans (animals). This surface may be epithelium (skin, respiratory tract, gastrointestinal tract, etc.), mesothelium (pleural cavity, peritoneal cavity, pericardial cavity, etc.) and endothelium (blood vessels, lymph vessels, etc.)

Structure

As seen with the electron microscope, the basement membrane is composed of two layers, the basal lamina and the underlying layer of reticular connective tissue. The underlying connective tissue attaches to the basal lamina with collagen VII anchoring fibrils and fibrillin microfibrils. The two layers together are collectively referred to as the basement membrane.

The basal lamina layer can further be divided into two layers. The clear layer closer to the epithelium is called the lamina lucida, while the dense layer closer to the connective tissue is called the lamina densa. The electron-dense lamina densa membrane is about 30–70 nanometers thick, and consists of an underlying network of reticular collagen IV fibrils which average 30 nanometers in diameter and 0.1–2 micrometers in thickness. In addition to collagen, this supportive matrix contains intrinsic macromolecular components. The lamina densa, whose collagen IV fibers are coated with the heparan sulfate-rich proteoglycan perlecan, and the lamina lucida (made up of laminin, integrins, entactins, and dystroglycans) together make up the basal lamina.

Integrins are not part of the basal lamina, they are part of desmosomes which are in the basement membrane but not the basal lamina.

To represent the above in a visually organised manner, the basement membrane is organized as follows:

• Epithelial/mesothelial/endothelial tissue (outer)

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• Basement membrane
  • Basal lamina
    • Lamina lucida
      • laminin
      • integrins (hold to base)
      • nidogens
      • dystroglycans
    • Lamina densa
      • collagen IV (coated with perlecan, rich in heparan sulfate)
  • Attaching proteins (between the basal and reticular laminae)
    • collagen VII (anchoring fibrils)
    • fibrillin (microfibrils)
  • Lamina reticularis
    • collagen III (as reticular fibers)

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• Connective tissue (Lamina propria)

Function

The primary function of the basement membrane is to anchor down the epithelium to its loose connective tissue (the dermis or lamina propria) underneath. This is achieved by cell-matrix adhesions through substrate adhesion molecules (SAMs).

The basement membrane acts as a mechanical barrier, preventing malignant cells from invading the deeper tissues. Early stages of malignancy that are thus limited to the epithelial layer by the basement membrane are called carcinoma in situ.

The basement membrane is also essential for angiogenesis (development of new blood vessels). Basement membrane proteins have been found to accelerate differentiation of endothelial cells.

The most notable examples of basement membranes are:

• the glomerular basement membrane of the kidney, by the fusion of the basal lamina from the endothelium of glomerular capillaries and the podocyte basal lamina,
• between lung alveoli and pulmonary capillaries, by the fusion of the basal lamina of the lung alveoli and of the basal lamina of the lung capillaries, which is where oxygen and CO₂ diffusion happens.

As of 2017 many other roles for basement membrane have been found that include blood filtration and muscle homeostasis.

Clinical significance

Some diseases result from a poorly functioning basement membrane. The cause can be genetic defects, injuries by the body's own immune system, or other mechanisms. Diseases involving basement membranes at multiple locations include:

• Genetic defects in the collagen fibers of the basement membrane, including Alport syndrome and Knobloch syndrome
• Autoimmune diseases targeting basement membranes. Non-collagenous domain basement membrane collagen type IV is autoantigen (target antigen) of autoantibodies in the autoimmune disease Goodpasture's syndrome.
• A group of diseases stemming from improper function of basement membrane zone are united under the name epidermolysis bullosa.

In histopathology, a thickened basement membrane indicates mainly systemic lupus erythematosus or dermatomyositis, but also possibly lichen sclerosus.