Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis

Hamid Bakshi, Murtaza M Tambuwala

Research output: Contribution to journalArticle

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 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.
LanguageEnglish
JournalInflammation
Early online date3 Aug 2019
DOIs
Publication statusE-pub ahead of print - 3 Aug 2019

Fingerprint

Prolyl Hydroxylases
Colitis
Disease Progression
Inflammatory Bowel Diseases
Prolyl-Hydroxylase Inhibitors
Protein Isoforms
Theoretical Models
Control Groups

Keywords

  • colitis
  • Prolyl hydroxylase
  • In vivo

Cite this

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title = "Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis",
abstract = "Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors areshown to be protective in several models of inflammatory bowel disease (IBD).However, these non-selective inhibitors are known to inhibit all the three isoforms ofPHD i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated theassociated changes in levels of PHDs during the development and recovery ofchemically 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 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.",
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Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis. / Bakshi, Hamid ; Tambuwala, Murtaza M.

03.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Bakshi, Hamid

AU - Tambuwala, Murtaza M

PY - 2019/8/3

Y1 - 2019/8/3

N2 - Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors areshown to be protective in several models of inflammatory bowel disease (IBD).However, these non-selective inhibitors are known to inhibit all the three isoforms ofPHD i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated theassociated changes in levels of PHDs during the development and recovery ofchemically 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 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.

AB - Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors areshown to be protective in several models of inflammatory bowel disease (IBD).However, these non-selective inhibitors are known to inhibit all the three isoforms ofPHD i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated theassociated changes in levels of PHDs during the development and recovery ofchemically 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 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.

KW - colitis

KW - Prolyl hydroxylase

KW - In vivo

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