Trefoil factors (TFF) are multi-functional peptides that are synthesized and secreted by mucin-secreting epithelial cells in amphibians and vertebrates. They are highly conserved in evolution, and are characterized by heat and enzymatic digestion resistance. Mammalian TFFs have three members (TFF1-3), the gastric peptides pS2/TFF1 and spasmolytic peptide (SP)/TFF2, and the intestinal trefoil factor (ITF)/TFF3. The gastrointestinal tract and the airway system are major organs of their expression and secretion. Since the identification of mammalian TFF3 in 1991, many evidence have suggested that TFF3 is involved in the pathological processes of several human diseases, such as mucosal disorders and cancer. In clinical medicine, TFF is primarily applied as drugs in the mucosal protection, in the prevention and the treatment of mucosal damage-related diseases and as pathological biomarkers of tumors. But, it has also been generally accepted that the hypothesis of TFF3 as a biomarker needs more clinical trails.

Accordingly, Prof. ZHANG Yun (Kunming Institute of Zoology, CAS) and his team have conducted a large prospective randomized study of 1,071 Chinese patients, recently, and their results strongly supported the positive correlation tendency between serum and urine TFF3 concentrations and the severity of chronic kidney disease (CKD).

“Our data collected from this large scaled clinical trail has reveal the necessarily of considering kidney injuries when performing clinical TFF3 research and we believe that the further studies of TFF3 in CKD will help us in understanding its pathological roles in other diseases”, Prof. ZHANG said.

The biological roles of TFF families are one of the long term research interests of Prof. ZHANG’s team. In 2011 and 2012, they have conducted studies to elucidate the relationships of frog trefoil factor (TFF) 2 and human TFF2 with their correlated protease-activated receptors and their underlining mechanisms.

In this most recent research, by collaborating with Dr. LUO Huiming (The First People’s Hospital of Yunnan Province), the mean serum concentrations of TFF3 in patients with CKD, metastatic and secondary carcinoma and acute gastroenteritis were measured interpedently. Compared with patients with other common clinical diseases, these item values were all significantly high. Based on the widely accepted concept that TFF plays an important role in mucosal protection and wound healing, and combined with the further matched case-control study, Prof. ZHANG concluded that the increased TFF3 concentration in serum and urine might by secreted from renal tubular epithelial cells in damages kidneys.

Corroborating with other studies, this new finding could accelerate pathomechanism research and the development of TFFs for clinical diagosistic practices. The full text could be obtained from PLoS One (http://dx.plos.org/10.1371/journal.pone.0080271)