Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications

Lan Wei; Jingjing Gao; Liangzhi Wang; Qianru Tao; Chao Tu

doi:10.1177/20420188231220134

Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications

Ther Adv Endocrinol Metab. 2023 Dec 25:14:20420188231220134. doi: 10.1177/20420188231220134. eCollection 2023.

Authors

Lan Wei¹, Jingjing Gao², Liangzhi Wang¹, Qianru Tao³, Chao Tu⁴

Affiliations

¹ Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
² Zhonglou District Center for Disease Control and Prevention, Changzhou, Jiangsu, China.
³ Department of Nephrology, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, 213000, Jiangsu, China.
⁴ Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, 213000, Jiangsu, China.

Abstract

Diabetic angiopathy, which includes diabetic kidney disease (DKD), cardio-cerebrovascular disease, and diabetic retinopathy (DR) among other diseases, is one of the most common complications affecting diabetic patients. Among these, DKD, which is a major cause of morbidity and mortality, affects about 40% of diabetic patients. Similarly, DR involves retinal neovascularization and neurodegeneration as a result of chronic hyperglycemia and is the main cause of visual impairment and blindness. In addition, inflammation also promotes atherosclerosis and diabetes, with atherosclerosis-related cardiovascular diseases being often a main cause of disability or death in diabetic patients. Given that vascular diseases caused by diabetes negatively impact human health, it is therefore important to identify appropriate treatments. In this context, some studies have found that the Hippo/Yes-associated protein (YAP) pathway is a highly evolutionarily conserved protein kinase signal pathway that regulates organ growth and size through its effector signaling pathway Transcriptional co-Activator with PDZ-binding motif (TAZ) and its YAP. YAP is a key factor in the Hippo pathway. The activation of YAP regulates gluconeogenesis, thereby regulating glucose tolerance levels; silencing the YAP gene thereby prevents the formation of glomerular fibrosis. YAP can combine with TEA domain family members to regulate the proliferation and migration of retinal vascular endothelial cells (ECs), so YAP plays a prominent role in the formation and pathology of retinal vessels. In addition, YAP/TAZ activation and translocation to the nucleus promote endothelial inflammation and monocyte-EC attachment, which can increase diabetes-induced cardiovascular atherosclerosis. Hippo/YAP signaling pathway provides a potential therapeutic target for diabetic angiopathy, which can prevent the progression of diabetes to DR and improve renal fibrosis and cardio-vascular atherosclerosis.

Keywords: Hippo/YAP pathway; atherosclerosis; diabetic kidney disease; diabetic retinopathy.

Publication types

Review