Amphiregulin, also known as AREG, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

synthesized as a transmembrane glycoprotein with 252 aminoacids and it is encoded by the ''AREG''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. in humans.

Function

The protein encoded by this gene is a member of the

epidermal growth factor Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds. EGF was originally de ...

(EGF) family. It is a critical

autocrine Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with p ...

growth factor as well as a

mitogen A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a ...

for

astrocyte Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...

Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ...

s, and

fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...

s. It is ligand for

(EGF) and it is related to

transforming growth factor alpha Transforming growth factor alpha (TGF-α) is a protein that in humans is encoded by the TGFA gene. As a member of the epidermal growth factor (EGF) family, TGF-α is a mitogenic polypeptide. The protein becomes activated when binding to receptors ...

(TGF-alpha). This protein interacts with the

Epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor rec ...

(EGFR) to promote the growth of normal epithelial cells.

Biological role

AREG is a critical factor in estrogen action and

ductal Lafarge is a French industrial company specialising in cement, construction aggregates, and concrete. It is the world's largest cement manufacturer. It was founded in 1833 by Joseph-Auguste Pavin de Lafarge and is a part of the Holcim Group. I ...

development of the

mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in pr ...

s. Amphiregulin has been found to be essential for mammary ductal development, as evidenced by absence of ductal growth in amphiregulin

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

. This is similar to the

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

s of EGFR and

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex h ...

knockout mice, which also show absence of ductal growth. Amphiregulin is expressed in many parts of body such as ovaries, placenta, pancreas, breasts, lungs and spleen. Expression of amphiregulin can be induced by TGF-α, TNF-α, interleukin 1, and prostaglandins.

Clinical significance

Psoriasis

Mutations in this encoded protein are associated with a

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complet ...

-like skin phenotype. Higher circulating levels of amphiregulin are associated with AGVHD progression.

Cancer

Overexpression of amphiregulin is connected with cancer of the breast, prostate, colon, pancreas, lung, spleen, and bladder.

Rheumatoid arthritis

It seems that expression of AREG is connected with proliferation of fibroblasts and production of proinflammatory cytokines interleukin 8 and vascular endothelial growth factor (VEGF).

Inflammation

Amphiregulin is part of cellular response type 2. It was found that the cell source of amphiregulin is innate lymphoid cells 2 (ILC2) which are dependent on interleukin 33. ILC2 expressed amphiregulin after tissue damage of the intestines and activation by IL-33. Moreover, endogenous AREG with IL-33 decreased the intestinal inflammation in mice with normal count of T-lymphocytes and in deficient mice.

References

External links

* * * {{Growth factor receptor modulators Estrogen regulation