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The basement membrane is a thin, pliable sheet-like type of
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...
that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and
endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...
, and the underlying connective tissue.


Structure

As seen with the
electron microscope An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
, the basement membrane is composed of two layers, the basal lamina and the reticular lamina. The underlying connective tissue attaches to the basal lamina with
collagen VII Collagen alpha-1(VII) chain is a protein that in humans is encoded by the ''COL7A1'' gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epide ...
anchoring fibrils and
fibrillin Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue. Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, whic ...
microfibril A microfibril is a very fine fibril, or fiber-like strand, consisting of glycoproteins and cellulose. It is usually, but not always, used as a general term in describing the structure of protein fiber, e.g. hair and sperm tail. Its most frequently ...
s. The basal lamina layer can further be subdivided into two layers based on their visual appearance in electron microscopy. The lighter-colored layer closer to the epithelium is called the lamina lucida, while the denser-colored layer closer to the connective tissue is called the lamina densa. The electron-dense lamina densa layer is about 30–70 nanometers thick and consists of an underlying network of reticular
collagen IV Collagen IV (ColIV or Col4) is a type of collagen found primarily in the basal lamina. The collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rather than in parallel. Also, ...
fibrils which average 30 nanometers in diameter and 0.1–2 micrometers in thickness and are coated with the heparan sulfate-rich proteoglycan
perlecan Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the ''HSPG2'' gene. The HSPG2 gene codes for a 4,391 ami ...
. In addition to collagen, this supportive matrix contains intrinsic macromolecular components. The lamina lucida layer is made up of
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...
,
integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle ...
s, entactins, and dystroglycans. Integrins are a key component of
hemidesmosome Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach t ...
s which serve to anchor the epithelium to the underlying basement membrane. To represent the above in a visually organised manner, the basement membrane is organized as follows: *
Epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
/ mesothelial/
endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
tissue (outer) * Basement membrane ** Basal lamina *** Lamina lucida ****
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...
****
integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle ...
s (
hemidesmosome Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach t ...
s) **** nidogens **** dystroglycans *** Lamina densa ****
collagen IV Collagen IV (ColIV or Col4) is a type of collagen found primarily in the basal lamina. The collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rather than in parallel. Also, ...
(coated with
perlecan Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the ''HSPG2'' gene. The HSPG2 gene codes for a 4,391 ami ...
, rich in
heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...
) ** Attaching proteins (between the basal and reticular laminae) ***
collagen VII Collagen alpha-1(VII) chain is a protein that in humans is encoded by the ''COL7A1'' gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epide ...
(anchoring fibrils) ***
fibrillin Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue. Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, whic ...
(
microfibril A microfibril is a very fine fibril, or fiber-like strand, consisting of glycoproteins and cellulose. It is usually, but not always, used as a general term in describing the structure of protein fiber, e.g. hair and sperm tail. Its most frequently ...
s) ** Lamina reticularis *** collagen III (as
reticular fibers Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a supportin ...
) * 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 Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
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 Carcinoma ''in situ'' (CIS) is a group of abnormal cells. While they are a form of neoplasm, there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, bre ...
. The basement membrane is also essential for angiogenesis (development of new blood vessels). Basement membrane proteins have been found to accelerate differentiation of
endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
cells. The most notable examples of basement membranes is the glomerular basement membrane of the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
, by the fusion of the basal lamina from the
endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...
of glomerular capillaries and the podocyte basal lamina, and between lung alveoli and pulmonary
capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
, 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 diffusion occurs (
gas exchange Gas exchange is the physical process by which gases move passively by diffusion across a surface. For example, this surface might be the air/water interface of a water body, the surface of a gas bubble in a liquid, a gas-permeable membrane, or a ...
). As of 2017, other roles for basement membrane include blood filtration and muscle homeostasis. Fractones may be a type of basement membrane, serving as a niche for stem cells.


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 Alport syndrome is a genetic disorder affecting around 1 in 5,000-10,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect ...
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 Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited E ...
. In histopathology, a thickened basement membrane indicates mainly systemic lupus erythematosus or
dermatomyositis Dermatomyositis (DM) is a long-term inflammatory disorder which affects skin and the muscles. Its symptoms are generally a skin rash and worsening muscle weakness over time. These may occur suddenly or develop over months. Other symptoms may inc ...
, but also possibly
lichen sclerosus Lichen sclerosus (LS) is a chronic, inflammatory skin disease of unknown cause which can affect any body part of any person but has a strong preference for the genitals (penis, vulva) and is also known as balanitis xerotica obliterans (BXO) when ...
.


Origin

These are only found within diploblastic and homoscleromorphic sponge animals. The homoscleromorph were found to be sister to diploblasts in some studies, making the membrane originate once in the history of life. But more recent studies have disregarded diploblast-homoscleromorph group, so other sponges may have lost it (most probable) or the origin in the two groups may be separate.


See also

*


References


Further reading

* {{Authority control Angiology Tissues (biology) Histology