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首页> 外文期刊>Biochemical Pharmacology >The opioid growth factor-opioid growth factor receptor axis: Homeostatic regulator of cell proliferation and its implications for health and disease
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The opioid growth factor-opioid growth factor receptor axis: Homeostatic regulator of cell proliferation and its implications for health and disease

机译:阿片类生长因子-阿片类生长因子受体轴:细胞增殖的稳态调节剂及其对健康和疾病的影响

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摘要

The opioid growth factor (OGF), chemically termed [Met 5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G 1/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.
机译:阿片类生长因子(OGF),化学上称为[Met 5]-脑啡肽,是一种内源性阿片肽,可与OGF受体(OGFr)相互作用,通过调节细胞周期蛋白依赖性抑制激酶来延迟细胞周期的G 1 / S界面(CKI)途径。 OGF-OGFr轴是一种有声调的抑制性途径,是体内稳态和再上皮化过程中的重要调节剂,并且在自身免疫性疾病和癌症的发作和发展中发挥作用。 OGF-OGFr轴的调节可通过多种药理和分子方法来完成,包括使用阿片类药物拮抗剂纳曲酮的间歇或连续暴露,OGFr表达的遗传操作以及OGF的抗体中和。在临床上,OGF是一种生物疗法,在治疗癌症方面具有潜在的应用。目前,正在评估低剂量纳曲酮用于治疗自身免疫性疾病,例如克罗恩氏病和多发性硬化症。高剂量的纳曲酮可有效逆转干眼症,并促进正常和糖尿病大鼠角膜擦伤的修复;这些研究正在临床中进行研究。纳曲酮还可以增强1型或2型糖尿病动物模型中的全层伤口闭合,并且计划将此知识应用于临床。总而言之,将OGF-OGFr轴理解为稳态的增殖调节剂对于维持人类健康和治疗疾病具有重要意义。

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