Upregulated expression of hITF in Crohn's disease and screening of hITF Interactant by a yeast two-hybrid system

Dig Dis Sci. 2010 Oct;55(10):2929-39. doi: 10.1007/s10620-010-1227-0. Epub 2010 May 26.

Abstract

Aims: To study the expression of human intestinal trefoil factor (hITF) mRNA in Crohn's disease and to screen the cellular proteins that can interact with the hITF protein by a yeast two-hybrid system in order to explore the mechanism of hITF in protecting intestinal mucosa from injury.

Methods: Seventy-eight patients underwent double-balloon enteroscopy (DBE). Expression of hITF mRNA was detected by quantitative real-time polymerase chain reaction analysis (qRT-PCR). The hITF gene was amplified by PCR and cloned into vector pDEST32. The yeast cells cotransformed with pDEST32-hITF and the human jejunal cDNA library were plated in a selective SC-Leu-Trp-His-Ura medium. The subsequent screen was performed with χ-gal detection, and true-positive clones were sequenced and analyzed with bioinformatics. Co-immunoprecipitation (Co-IP) was performed to confirm the binding of putative proteins to the hITF protein.

Results: Thirty-nine patients were diagnosed with Crohn's disease. We found that the expression of hITF mRNA is significantly increased in Crohn's disease compared to normal controls. A total of ten colonies were selected and sequenced. Among these, six colonies were Homo sapiens zinc finger protein 193 (ZNF193), three colonies were Homo sapiens Aldo-keto reductase family 1C 1 (AKR1C1), and one colony was of an unknown gene. A reverse two-hybrid experiment and Co-IP indicated that ZNF193 and AKR1C1 might interact with hITF.

Conclusions: The expression of hITF mRNA is increased in Crohn's disease. ZNF193 and AKR1C1 are proteins that can interact with the hITF protein by a yeast two-hybrid system and Co-IP, hITF may contribute to the mucosal repair through this interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism
  • Crohn Disease / pathology
  • Gene Expression / physiology
  • Gene Library
  • Genetic Testing / methods*
  • Homeostasis / physiology
  • Humans
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology
  • Jejunum / pathology
  • Jejunum / physiology
  • Kidney / cytology
  • Peptides / genetics*
  • Plasmids / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trefoil Factor-2
  • Two-Hybrid System Techniques*
  • Up-Regulation / physiology

Substances

  • Peptides
  • RNA, Messenger
  • Trefoil Factor-2