Diabetic Kidney Disease-Associated Pathological Angiogenesis: The Role of Aquaporin-1

Abstract

Diabetic kidney disease (DKD) is recognized as one of the leading causes of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide, representing a rapidly growing global public health concern. Despite significant advances in understanding the complex pathophysiological mechanisms of DKD, curative treatments are currently unavailable, and the reversal of established renal injury remains an elusive goal in clinical practice. Among various pathological features, aberrant angiogenesis has been closely associated with glomerular injury and the early development of proteinuria in DKD, playing a crucial role in driving disease progression. However, the molecular mechanisms underlying this pathological angiogenesis in DKD remain incompletely understood and warrant further elucidation. Recent research has increasingly implicated aquaporins (AQPs), a family of transmembrane water channel proteins, in the pathogenesis of both acute and chronic kidney disorders, including DKD. In particular, aquaporin-1 (AQP1), which is highly expressed in renal tissues, has emerged as a potential modulator of angiogenic activity within the kidney microenvironment. Although AQP1 and aberrant angiogenesis have been individually explored in the context of DKD, no comprehensive review has systematically examined their interrelationship. This review consolidates current evidence regarding the role of AQP1 in pathological angiogenesis during DKD progression, highlighting its potential significance and identifying gaps that warrant further investigation.