4.6 Article

Trefoil factor 3: New highlights in chronic kidney disease research

Journal

CELLULAR SIGNALLING
Volume 100, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2022.110470

Keywords

Trefoil factor 3; Chronic kidney disease; Renal tubular epithelial cell; Gut -kidney axis; Signaling

Categories

Funding

  1. Key Project of National Natural Science Foundation of China [81830113]
  2. National Key R & D Plan Research on Modernization of Traditional Chinese Medicine [2018YFC1704200]
  3. Major Basic and Applied Basic Research Projects of Guangdong Province of China [2019B030302005]
  4. Basic and Applied Basic Research Project of Guangzhou [202102011330130006]
  5. National Natural Science Foundation of China [82204704]
  6. Medical Science and Technology Foundation of Guangdong Province [B2020023]

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TFF3 has various biological functions in the kidney, particularly playing an important role in chronic kidney disease. Research suggests that the levels of TFF3 in urine and serum significantly increase with the progression of CKD.
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.

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