The opioid growth factor-opioid growth factor receptor axis: Homeostatic regulator of cell proliferation and its implications for health and disease

Research output: Contribution to journalComment/debate

38 Citations (Scopus)

Abstract

The opioid growth factor (OGF), chemically termed [Met5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G1/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF. Clinically, OGF is a biological therapy that has potential application for treatment of cancer. Currently, naltrexone at low dosages is being evaluated for treatment of autoimmune diseases such as Crohn's and multiple sclerosis. High dosages of naltrexone are effective in reversing dry eye and accelerating the repair of corneal abrasions in normal and diabetic rats; these studies are under investigation in the clinical setting. Naltrexone also enhances full-thickness wound closure in animal models of Type 1 or Type 2 diabetes, and translation of this knowledge to the clinic is planned. In summary, understanding the OGF-OGFr axis as a homeostatic regulator of proliferation has substantial implications for maintaining human health and treatment of disease.

Original languageEnglish (US)
Pages (from-to)746-755
Number of pages10
JournalBiochemical Pharmacology
Volume84
Issue number6
DOIs
StatePublished - Sep 15 2012

Fingerprint

Cell proliferation
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
Naltrexone
Cell Proliferation
Health
Autoimmune Diseases
Opioid Peptides
Narcotic Antagonists
Enkephalins
Re-Epithelialization
Medical problems
Abrasion
Biological Therapy
Translational Medical Research
Cyclin-Dependent Kinases
methionine-enkephalin receptor
Rats
Animals
Repair

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

@article{535a0c8d230546a3bb7bc061b66d1d66,
title = "The opioid growth factor-opioid growth factor receptor axis: Homeostatic regulator of cell proliferation and its implications for health and disease",
abstract = "The opioid growth factor (OGF), chemically termed [Met5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G1/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF. Clinically, OGF is a biological therapy that has potential application for treatment of cancer. Currently, naltrexone at low dosages is being evaluated for treatment of autoimmune diseases such as Crohn's and multiple sclerosis. High dosages of naltrexone are effective in reversing dry eye and accelerating the repair of corneal abrasions in normal and diabetic rats; these studies are under investigation in the clinical setting. Naltrexone also enhances full-thickness wound closure in animal models of Type 1 or Type 2 diabetes, and translation of this knowledge to the clinic is planned. In summary, understanding the OGF-OGFr axis as a homeostatic regulator of proliferation has substantial implications for maintaining human health and treatment of disease.",
author = "Patricia McLaughlin and Ian Zagon",
year = "2012",
month = "9",
day = "15",
doi = "10.1016/j.bcp.2012.05.018",
language = "English (US)",
volume = "84",
pages = "746--755",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - The opioid growth factor-opioid growth factor receptor axis

T2 - Homeostatic regulator of cell proliferation and its implications for health and disease

AU - McLaughlin, Patricia

AU - Zagon, Ian

PY - 2012/9/15

Y1 - 2012/9/15

N2 - The opioid growth factor (OGF), chemically termed [Met5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G1/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF. Clinically, OGF is a biological therapy that has potential application for treatment of cancer. Currently, naltrexone at low dosages is being evaluated for treatment of autoimmune diseases such as Crohn's and multiple sclerosis. High dosages of naltrexone are effective in reversing dry eye and accelerating the repair of corneal abrasions in normal and diabetic rats; these studies are under investigation in the clinical setting. Naltrexone also enhances full-thickness wound closure in animal models of Type 1 or Type 2 diabetes, and translation of this knowledge to the clinic is planned. In summary, understanding the OGF-OGFr axis as a homeostatic regulator of proliferation has substantial implications for maintaining human health and treatment of disease.

AB - The opioid growth factor (OGF), chemically termed [Met5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G1/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF. Clinically, OGF is a biological therapy that has potential application for treatment of cancer. Currently, naltrexone at low dosages is being evaluated for treatment of autoimmune diseases such as Crohn's and multiple sclerosis. High dosages of naltrexone are effective in reversing dry eye and accelerating the repair of corneal abrasions in normal and diabetic rats; these studies are under investigation in the clinical setting. Naltrexone also enhances full-thickness wound closure in animal models of Type 1 or Type 2 diabetes, and translation of this knowledge to the clinic is planned. In summary, understanding the OGF-OGFr axis as a homeostatic regulator of proliferation has substantial implications for maintaining human health and treatment of disease.

UR - http://www.scopus.com/inward/record.url?scp=84864953326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864953326&partnerID=8YFLogxK

U2 - 10.1016/j.bcp.2012.05.018

DO - 10.1016/j.bcp.2012.05.018

M3 - Comment/debate

C2 - 22687282

AN - SCOPUS:84864953326

VL - 84

SP - 746

EP - 755

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 6

ER -