Regenerating protein family

Last updated

The regenerating protein family often abbreviated as Reg family are a group of small secretory proteins that are involved in the proliferation and differentiation of diverse cell types. [1] [2] In addition they are important in protecting cells from death caused by damage or inflammation.

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 reticulum.

Contents

Family members

There are seven types of Reg genes present in the mouse mainly located on chromosome 6 but only five (REG1A, REG1B, REG3A, REG3G, and REG4) have been shown to be present in the human on chromosome 2. [3]

REG1A protein-coding gene in the species Homo sapiens

Lithostathine-1-alpha also known as islet cells regeneration factor (ICRF) or islet of Langerhans regenerating protein (REG) is a protein that in humans is encoded by the REG1A gene.

REG1B protein-coding gene in the species Homo sapiens

Lithostathine-1-beta is a protein that in humans is encoded by the REG1B gene.

REG3A protein-coding gene in the species Homo sapiens

Regenerating islet-derived protein 3 alpha formerly known as HIP/PAP and peptide 23 is a protein that in humans is encoded by the REG3A gene.

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, lectins, antiapoptotic factors or growth factors for pancreatic β-cells, neural cells and epithelial cells in the digestive system. [4]

These C-type lectins contain a single carbohydrate recognition domain and once secreted, these soluble proteins act in an autocrine and/or paracrine 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 REG1A and REG1B are associated with various diseases such as diabetes and gastrointestinal cancer. Reg expression has been associated with islet regeneration in pancreas [5] that may be important for islet transplantation and for diabetes therapy and for cancer studies.

The mouse Reg1, Reg2, and Reg3δ, expressed by β-cells and acinar 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 adjuvant treatment. [6] This is related to the induction of Th17 cells by adjuvant treatment and these cells produce Interleukin-22 (IL-22). Pancreatic islets express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration. [7]

An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents. Adjuvants may be added to a vaccine to boost the immune response to produce more antibodies and longer-lasting immunity, thus minimizing the dose of antigen needed. Adjuvants may also be used to enhance the efficacy of a vaccine by helping to modify the immune response to particular types of immune system cells: for example, by activating T cells instead of antibody-secreting B cells depending on the purpose of the vaccine. Adjuvants are also used in the production of antibodies from immunized animals. There are different classes of adjuvants that can push immune response in different directions, but the most commonly used adjuvants include aluminum hydroxide and paraffin oil.

Pancreatic islets regions of the pancreas

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 to 2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose.

Related Research Articles

Interleukin 1 beta protein-coding gene in the species Homo sapiens

Interleukin 1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.

Interleukin 22 protein-coding gene in the species Homo sapiens

Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.

Interleukin 8 receptor, alpha protein-coding gene in the species Homo sapiens

Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD181. The IUPHAR Committee on Receptor Nomenclature and Drug Classification use the HGNC recommended name, CXCR1.

PDX1 A protein involved in the pancreas and duodenum differentiation

PDX1, also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster. In vertebrates, Pdx1 is necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1. The gene was originally identified in the clawed frog Xenopus laevis and is present in many species across the bilaterian phylogeny. In particular, PDX1 orthologs have been identified in most mammals.

Interleukin 1 receptor, type II protein-coding gene in the species Homo sapiens

Interleukin 1 receptor, type II (IL-1R2) also known as CD121b is an interleukin receptor. IL1R2 also denotes its human gene.

Interleukin 12 receptor, beta 2 subunit protein-coding gene in the species Homo sapiens

Interleukin 12 receptor, beta 2 subunit is a subunit of the interleukin 12 receptor. IL12RB2 is its human gene. IL12RB2 orthologs have been identified in all mammals for which complete genome data are available.

Interleukin-21 receptor protein-coding gene in the species Homo sapiens

Interleukin 21 receptor is a type I cytokine receptor. IL21R is its human gene.

Neurogenins are a family of bHLH transcription factors involved in specifying neuronal differentiation. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.

IL2RB protein-coding gene in the species Homo sapiens

Interleukin-2 receptor subunit beta is a protein that in humans is encoded by the IL2RB gene. Also known as CD122; IL15RB; P70-75.

Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas. The islets containing the pancreatic β-cells, and in some cases, the exocrine tissues, become infiltrated by T and B lymphocytes, macrophages and dendritic cells. This innate immune cell and lymphocyte infiltration can result in destruction of the insulin producing beta cells of the islets, and clinical diabetes. Insulitis is often studied in the multiple low dose streptozotocin (MLDS) mouse model or the non-obese diabetic (NOD) mouse model of type 1 diabetes. The chemokine family of proteins may play a key role in promoting leukocytic infiltration into the pancreas prior to pancreatic beta-cell destruction.

REG3G protein-coding gene in the species Homo sapiens

Regenerating islet-derived protein 3 gamma is a protein that in humans is encoded by the REG3G gene.

Neurogenin-3 protein-coding gene in the species Homo sapiens

Neurogenin-3 is a protein that in humans is encoded by the NEUROG3 gene.

Freund's adjuvant is a solution of antigen emulsified in mineral oil and used as an immunopotentiator (booster). The complete form, Freund's Complete Adjuvant is composed of inactivated and dried mycobacteria, whereas the incomplete form lacks the mycobacterial components. It is named after Jules T. Freund.

Helper T cells are essential part of body's immune system. These cells are divided in many subsets based upon their ability to produce different cytokines. Following the discovery of interleukin-17 (IL-17) producing T helper (Th17) cells as a distinct lineage of T helper cells it became clear that these cells play an important role in the host defense and participate in the pathogenesis of many inflammatory and autoimmune diseases. The Th17 cells can alter their differentiation program ultimately giving rise to either protective or pro-inflammatory pathogenic cells. The protective and non-pathogenic Th17 cells are termed as Treg17 cells.

Pancreatic progenitor cell

Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas.

Pancreatic islet macrophage

Islet resident macrophages are the predominant myeloid cell of the pancreatic islets of langerhans.

References

  1. ↑ Parikh A, Stephan AF, Tzanakakis ES (2012). "Regenerating proteins and their expression, regulation and signaling". Biomol Concepts. 3 (1): 57–70. doi:10.1515/bmc.2011.055. PMC   3348543  Lock-green.svg. PMID   22582090.
  2. ↑ Jin CX, Hayakawa T, Ko SB, Ishiguro H, Kitagawa M (2011). "Pancreatic stone protein/regenerating protein family in pancreatic and gastrointestinal diseases". Intern. Med. 50 (15): 1507–16. doi:10.2169/internalmedicine.50.5362. PMID   21804274.
  3. ↑ Liu JL, Cui W, Li B, Lu Y (2008). "Possible roles of reg family proteins in pancreatic islet cell growth". Endocr Metab Immune Disord Drug Targets. 8 (1): 1–10. doi:10.2174/187153008783928361. PMID   18393918.
  4. ↑ Okamoto H (1999). "The Reg gene family and Reg proteins: with special attention to the regeneration of pancreatic beta-cells". J Hepatobiliary Pancreat Surg. 6 (3): 254–62. doi:10.1007/s005340050115. PMID   10526060.
  5. ↑ Singh B, Hill T, Krougly O, et al. (2013). "Role of IL-22 in tissue regeneration in autoimmunity". J. Immunol. 190 (Meeting Abstract Supplement): P5164.
  6. ↑ Huszarik K, Wright B, Keller C, Nikoopour E, Krougly O, Lee-Chan E, Qin HY, Cameron MJ, Gurr WK, Hill DJ, Sherwin RS, Kelvin DJ, Singh B (2010). "Adjuvant immunotherapy increases beta cell regenerative factor Reg2 in the pancreas of diabetic mice". J. Immunol. 185 (9): 5120–9. doi:10.4049/jimmunol.1001596. PMID   20876350.
  7. ↑ Hill T, Krougly O, Nikoopour E, Bellemore S, Lee-Chan E, Fouser LA, Hill DJ, Singh B (2013). "The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes". Cell Regeneration. 2 (1): 1–11. doi:10.1186/2045-9769-2-2. PMC   4230743  Lock-green.svg. PMID   25408874.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.