Aldose Reductase Involvement in EMT: Emerging Insights and Current Proposed Molecular Mechanisms

Aldose reductase (AKR1B1) is a member of the aldo-keto reductase (AKR) family and plays a variety of roles in many metabolic and physiological processes. Although its function in the polyol pathway and defense against reactive carbonyl species is well-documented, many of aldose reductase’s roles remain poorly understood. Recently, accumulating evidence has suggested a strong correlation between aldose reductase expression and/or activity and the epithelial-to-mesenchymal transition (EMT), a process fundamental to both physiological conditions (e.g., embryonic development and wound healing) and pathological states (such as fibrosis and metastasis). Specifically, aldose reductase appears to be a potent promoter of EMT in both tumor and non-tumor contexts, although the molecular mechanisms through which it drives EMT remain unclear. This review aims to summarize the growing body of studies highlighting the association between AKR1B1 and EMT, as well as to analyze the molecular mechanisms proposed by various authors. Finally, the main findings on EMT responses following AKR1B1 inhibition will be discussed, providing a comprehensive overview of current knowledge and identifying the critical gaps that must be addressed to fully elucidate the role of aldose reductase in this process.