In the present study, we demonstrated that activated JNK and Smad3 signaling pathways were co-localized in the tubulointerstitial compartment after FA-induced kidney damage, which provided rationale that blockade of both Smad3 and JNK signaling pathways may provide better protection from FA-induced progressive CKD than single blockade of Smad3 signaling or JNK signaling. Here, SMAD3 is linked to chronic kidney disease.