Circulating serum trefoil factor 3 (TFF3) is dramatically increased in chronic kidney disease

PLoS One. 2013 Nov 25;8(11):e80271. doi: 10.1371/journal.pone.0080271. eCollection 2013.

Abstract

Objectives: Trefoil factor 3 (TFF3) is a small peptide that plays an important role in mucosal protection, cell proliferation, and cell migration. The aberrant expression of TFF3 is correlated with gastrointestinal inflammation, solid tumors, and other clinical diseases. The objective of this study was to identify the distribution characteristics of serum TFF3 in common clinical diseases.

Materials and methods: A large prospective randomized study of 1,072 Chinese patients was performed using an enzyme-linked immunosorbent assay (ELISA) to examine the serum TFF3 concentrations in patients with different diseases. A matched case-control study was conducted on patients with chronic kidney disease (CKD) stages 1-5. Immunohistochemistry (IHC) was performed using renal tissues to determine the relationship between the severity of CKD and the serum and urine concentrations of TFF3 peptides.

Results: The mean serum concentrations of TFF3 in patients with CKD, metastatic and secondary carcinoma (MC) and acute gastroenteritis (AG) (200.9 ng/ml, 95.7 ng/ml and 71.7 ng/ml, respectively) were significantly higher than those in patients with other common clinical diseases. A positive correlation tendency was observed between the serum TFF3 concentrations and the severity of CKD. The mean serum TFF3 values for CKD stages 1-5 were 23.6 ng/ml, 29.9 ng/ml, 54.9 ng/ml, 85.0 ng/ml and 176.6 ng/ml, respectively. The same trend was observed in the urine TFF3 concentrations and the CKD stages. The creatinine(Cr)-corrected concentrations of TFF3 in urine were 367.1 ng/mg·Cr, 910.6 ng/mg·Cr, 1,149.0 ng/mg·Cr, 1,610.0 ng/mg·Cr and 3,475.0 ng/mg·Cr for CKD stages 1-5, respectively. IHC revealed that TFF3 expression was concentrated in tubular epithelial cells.

Conclusions: The influence of kidney injuries must be fully considered when performing clinical TFF3 research. Further studies on TFF3 in CKD will contribute to our understanding of its pathological roles and mechanisms in other diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / blood
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Kidney Tubules / metabolism
  • Neoplasm Metastasis / genetics
  • Peptides / blood*
  • Peptides / urine
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / genetics*
  • Trefoil Factor-3

Substances

  • Peptides
  • TFF3 protein, human
  • Trefoil Factor-3

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC-Yunnan joint funding U1132601, 31270835)¼Œthe National Basic Research Program of China (973 Program, 2010CB529800), and the key research program of the Chinese Academy of Sciences (KJZD-EW-L03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.