Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis

Hamid A. Bakshi, Vijay Mishra, Saurabh Satija, Meenu Mehta, Faruk L. Hakkim, Prashant Kesharwani, Kamal Dua, Dinesh K. Chellappan, Nitin B. Charbe, Garima Shrivastava, S. Rajeshkumar, Alaa A. Aljabali, Bahaa Al-trad, Kavita Pabreja, Murtaza M. Tambuwala

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Abstract

Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.

Original languageEnglish
Pages (from-to)2032-2036
Number of pages5
JournalInflammation
Volume42
Issue number6
Early online date3 Aug 2019
DOIs
Publication statusPublished - 1 Dec 2019

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Keywords

  • colitis
  • Prolyl hydroxylase
  • In vivo
  • prolyl hydroxylases
  • disease activity index
  • inflammatory bowel disease

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