Dysregulation of the OGF-OGFr pathway and associated diabetic complications.
Dysregulation of the OGF-OGFr pathway and associated diabetic complications.
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DOI：
10.33696/diabetes.3.041
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zagon IS
中科院分区：
文献类型：
--
作者：
McLaughlin PJ;Sassani JW;Zagon IS
糖尿病是一种全球性流行病，预计到2030年将有超过5.5亿人被诊断患有这种疾病。与糖尿病相关的并发症几乎影响所有系统，但超过54%的糖尿病患者患有眼表疾病，包括角膜病变，干眼或角膜表面敏感性改变，近70%的患者出现愈合缓慢的足部溃疡，如果不治疗，可能导致截肢。有新的信息与这些并发症相关的基础病理生理学，以及潜在的治疗。本评论汇集了临床前研究的数据，这些研究表明，糖尿病大鼠和小鼠的角膜表面并发症（如干眼和敏感性）以及角膜和皮肤上皮伤口愈合延迟与阿片样生长因子（OGF）-阿片样生长因子受体（OGFr）调节轴失调相关。该途径中的肽OGF，化学上称为[Met 5]-脑啡肽，在患有1型或2型糖尿病的人类和动物的血清中升高。该结果的原因尚不清楚。然而，有研究表明，阻断OGF（或OGF水平升高）及其受体之间的相互作用可以逆转，在某些情况下，可以预防糖尿病角膜并发症的发生。临床医生和医护人员需要认识到这一导致糖尿病并发症的基本病理生理学。在1型和2型糖尿病的多种动物模型中，OGF-OGFr生长调节系统的功能障碍在眼表面并发症和延迟皮肤伤口愈合并发症的发展中起作用。调节该系统可能有望逆转甚至预防人类的这些糖尿病并发症。此外，监测血清OGF水平应作为这些和其他糖尿病并发症发展的指标进行研究。
Diabetes is a worldwide epidemic with more than 550 million individuals expected to be diagnosed with the disease by 2030. Complications associated with diabetes affect nearly all systems, but more than 54% of diabetic individuals have ocular surface disorders including keratopathy, dry eye or altered corneal surface sensitivity, and nearly 70% experience slow healing foot ulcers which if left untreated, can lead to amputation. There is new information regarding the underlying pathophysiology associated with these complications, as well as potential treatment. This commentary assembles data on preclinical studies showing that corneal surface complications such as dry eye and sensitivity, as well as delayed epithelial wound healing in the cornea and skin in diabetic rats and mice, correlate with a dysregulation of the opioid growth factor (OGF)-opioid growth factor receptor (OGFr) regulatory axis. The peptide in this pathway, OGF, chemically termed [Met5]-enkephalin, is elevated in the serum of humans and animals with either type 1 or type 2 diabetes. The cause for this finding is unknown. However, there are studies that demonstrate that blockade of the interactions between OGF (or elevated levels of OGF) and its receptor can reverse and, in some cases, prevent the onset of diabetic corneal complications. Clinicians and healthcare workers need to recognize this fundamental pathophysiology leading to diabetic complications. Dysfunction of the OGF-OGFr growth regulatory system plays a role in the development of ocular surface complications and delayed cutaneous wound healing complications in multiple animal models of both Type 1 and Type 2 diabetes. Modulation of this system may hold promise for reversing or even preventing these diabetic complications in humans. Moreover, monitoring serum levels of OGF should be investigated as an indicator of the development of these and other diabetic complications.