The regenerating protein family often abbreviated as Reg family are a group of small

secretory protein A secretory protein is any protein, whether it be endocrine or exocrine, which is secreted by a cell. Secretory proteins include many hormones, enzymes, toxins, and antimicrobial peptides. Secretory proteins are synthesized in the endoplasmic ret ...

s that are involved in the proliferation and differentiation of diverse cell types. In addition they are important in protecting cells from death caused by damage or inflammation.

Family members

There are seven types of Reg genes present in the mouse mainly located on chromosome 6 but only five (

REG1A Pancreatic Stone Protein (PSP), also known as Lithostathine-1-alpha islet cells regeneration factor (ICRF) or islet of Langerhans regenerating protein (REG) is a protein that in humans is encoded by the ''REG1A'' gene as a single polypeptide of 144 ...

REG1B Lithostathine-1-beta is a protein that in humans is encoded by the ''REG1B'' gene. Function This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III ...

REG3A Regenerating islet-derived protein 3 alpha (or Regenerating islet-derived protein III-alpha) formerly known as HIP/PAP (Hepatocarcinoma-Intestine-Pancreas/Pancreatitis-Associated Protein) and peptide 23 is a protein that in humans is encoded by the ...

REG3G Regenerating islet-derived protein 3 gamma (also Regenerating islet-derived protein III-gamma) is a protein that in humans is encoded by the ''REG3G'' gene. Intestinal paneth cells produce REG3G (or REG3 gamma) via stimulation of toll-like recep ...

, and REG4) have been shown to be present in the human on chromosome 2.

Function

Reg proteins are involved in the growth and differentiation of cells from various organs under normal and disease conditions. These proteins function as

acute phase reactants Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the ''acute-p ...

lectins Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in r ...

, antiapoptotic factors or

growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for re ...

for pancreatic β-cells, neural cells and epithelial cells in the digestive system. These C-type lectins contain a single carbohydrate recognition domain and once secreted, these soluble proteins act in an

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 ...

and/or

paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse ove ...

manner to exert their effects on their cognate receptors, where they may stimulate an anti-microbial, anti-inflammatory, anti-apoptotic, or regenerative response depending on the tissue type. Cytokines such as IL-22 are major regulators of the expression of Reg proteins.

Clinical significance

Reg family members such as

and

are associated with various diseases such as diabetes and gastrointestinal cancer. Reg expression has been associated with islet regeneration in pancreas that may be important for

islet transplantation Islet transplantation is the transplantation of isolated islets from a donor pancreas into another person. It is an experimental treatment for type 1 diabetes mellitus. Once transplanted, the islets begin to produce insulin, actively regulating ...

and for diabetes therapy and for cancer studies. The mouse Reg1, Reg2, and Reg3δ, expressed by β-cells and

acinar An acinus (; plural, acini; adjective, acinar or acinous) refers to any cluster of cells that resembles a many-lobed "berry," such as a raspberry (''acinus'' is Latin for "berry"). The berry-shaped termination of an exocrine gland, where the ...

cells respectively, have been shown to be linked with pancreatic β-cell regeneration in the mouse by activating cyclin D1 and promoting β-cell cycle progression. Reg2 is substantially up-regulated in the pancreatic islets, particularly in the β-cells following

mycobacterial ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (''M. tuberculosis'') a ...

adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy Adjuvant therapy, also known ...

treatment. This is related to the induction of

Th17 T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differe ...

cells by adjuvant treatment and these cells produce

Interleukin-22 Interleukin-22 (IL-22) is protein that in humans is encoded by the ''IL22'' gene. Structure IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. IL-22R is expressed o ...

(IL-22).

Pancreatic islets The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of t ...

express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration.

References

{{Reflist, 35em Protein families