Proximal TGF-β Signaling in Chronic Injury: from a notorious fibrotic factor to a repair ally

Transforming growth factor beta (TGF-β) is a pleiotropic factor that plays a key role in the pathophysiology of chronic kidney disease (CKD). However, targeting TGF-β inhibition failed to mitigate CKD in practice. The proximal tubule (PT), the most vulnerable renal segment, plays a central role in post-injury repair or the drift to CKD. Despite its well-documented profibrotic effects, recent studies revealed benefits of TGF-β signaling in PT response to CKD, raising the question of its therapeutic potential. This review highlights mechanisms by which TGF-β signaling mediates the PT adaptive response to chronic injury and provides perspectives for developing novel CKD therapy.