How to inhibit transforming growth factor beta safely in diabetic kidney disease

Purpose of review Diabetic kidney disease (DKD) is a leading cause of mortality and morbidity in diabetes. This review aims to discuss the major features of DKD, to identify the difficult barrier encountered in developing a therapeutic strategy and to provide a potentially superior novel approach to retard DKD. Recent findings Renal inflammation and fibrosis are prominent features of DKD. Transforming growth factor beta (TGF beta) with its activity enhanced in DKD plays a key pathological profibrotic role in promoting renal fibrosis. However, TGF beta is a difficult drug target because it has multiple important physiological functions, such as immunomodulation. These physiological functions of TGF beta can be interrupted as a result of complete blockade of the TGF beta pathway if TGF beta is directly targeted, leading to catastrophic side-effects, such as fulminant inflammation. Cell division autoantigen 1 (CDA1) is recently identified as an enhancer of profibrotic TGF beta signaling and inhibitor of anti-inflammatory SIRT1. Renal CDA1 expression is elevated in human DKD as well as in rodent models of DKD. Targeting CDA1, by either genetic approach or pharmacological approach in mice, leads to concurrent attenuation of renal fibrosis and inflammation without any deleterious effects observed. Summary Targeting CDA1, instead of directly targeting TGF beta, represents a superior approach to retard DKD.

Automated summary

Targeting CDA1, instead of directly targeting TGF beta, represents a superior approach to retard DKD.