Trefoil factor 3: New highlights in chronic kidney disease research

Trefoil factor 3 (TFF3, also known as intestinal trefoil factor) is a small-molecule peptide containing a typical trefoil structure. TFF3 has several biological effects, such as wound healing, immune regulation, neuroprotection, and cell migration and proliferation promotion. Although TFF3 binding sites were identified in rat kidneys more than a decade ago, the specific effects of this small-molecule peptide on kidneys remain unclear. Until recently, much of the research on TFF3 in the kidney field has focused exclusively on its role as a biomarker. Notably, a large prospective randomized study of patients with 29 common clinical diseases revealed that chronic kidney disease (CKD) was associated with the highest serum TFF3 levels, which were 3-fold higher than in acute gastroenteritis, which had the second-highest levels. Examination of each stage of CKD revealed that urine and serum TFF3 levels significantly increased with the progression of CKD. These results suggest that the role of TFF3 in CKD needs further research. The present review summarizes the renal physiological expression, biological functions, and downstream signaling of TFF3, as well as the upstream events that lead to high expression of TFF3 in CKD.