Therapy for kidney fibrosis: is the Src kinase a potential target?

Abstract

Chronic kidney disease (CKD) is a public health challenge worldwide. As CKD is associated with high rates of morbidity and mortality, identification of novel targets for effective therapy is urgently needed. Yan et al. provide evidence that the Src kinase plays a critical role in the pathogenesis of CKD by integrating multiple fibrogenic signal inputs. Therefore, targeted inhibition of Src kinase may hold promise as a new strategy in the fight against CKD.

Figure 1. The Src kinase promotes fibroblast activation and kidney fibrosis by integrating multiple fibrogenic signal inputs

Upon stimulation by various extracellular cues such as transforming growth factor-β1 (TGF-β1), angiotensin II (Ang II), epidermal growth factor (EGF), or extracellular matrix (ECM), intracellular Src kinase is activated. Src activation leads to phosphorylation of the signaling proteins STAT3, AKT, and plasma membrane epidermal growth factor receptor (EGFR). Activation of Src also promotes TGF-β1–mediated Smad3 activation by multiple mechanisms (dashed line).