Wu Yuexiu, Chakrabarti Subrata
Department of Pathology, Schulich School of Medicine, Western University, London, Ontario, Canada.
Med Hypothesis Discov Innov Ophthalmol. 2015 Spring;4(1):17-26.
Diabetic retinopathy is the lead among causes of blindness in North America. Glucose-induced endothelial injury is the most important cause of diabetic retinopathy and other vascular complications. Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (BMK1), is a member of mitogen-activated protein kinases (MAPK) family. Physiologically, it is critical for cardiovascular development and maintenance of the endothelial cell integrity. Extracellular signal-regulated kinase 5 is protective for endothelial cells under stimulation and stress. Decreased activation of ERK5 results in increased endothelial cell death. Extracellular signal-regulated kinase 5 signaling may be subject to alteration by hyperglycemia, while signaling pathway including ERK5 may be subject to alteration during pathogenesis of diabetic complications. In this review, the role of ERK5 in diabetic macro- and microvascular complications with a focus on diabetic retinopathy are summarized and discussed.
糖尿病视网膜病变是北美失明的主要原因。葡萄糖诱导的内皮损伤是糖尿病视网膜病变和其他血管并发症的最重要原因。细胞外信号调节激酶5(ERK5),也称为大丝裂原活化蛋白激酶1(BMK1),是丝裂原活化蛋白激酶(MAPK)家族的成员。在生理上,它对心血管发育和内皮细胞完整性的维持至关重要。细胞外信号调节激酶5在刺激和应激下对内皮细胞具有保护作用。ERK5激活减少会导致内皮细胞死亡增加。细胞外信号调节激酶5信号可能会因高血糖而改变,而包括ERK5在内的信号通路可能在糖尿病并发症的发病过程中发生改变。在本综述中,总结并讨论了ERK5在糖尿病大血管和微血管并发症中的作用,重点是糖尿病视网膜病变。