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. 2019 Dec;42(6):2032-2036.
doi: 10.1007/s10753-019-01065-3.

Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis

Hamid A Bakshi  1 , Vijay Mishra  2 , Saurabh Satija  2 , Meenu Mehta  2 , Faruk L Hakkim  3 , Prashant Kesharwani  4 , Kamal Dua  5 , Dinesh K Chellappan  6 , Nitin B Charbe  7   8 , Garima Shrivastava  9 , S Rajeshkumar  10 , Alaa A Aljabali  11 , Bahaa Al-Trad  12 , Kavita Pabreja  13 , Murtaza M Tambuwala  14
Affiliations

Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis

Hamid A Bakshi et al. Inflammation. 2019 Dec.

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.

Keywords: colitis; disease activity index; inflammatory bowel disease; prolyl hydroxylases.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Changes in disease activity score (DAI) and colon length during active colitis. In a, the composite score of weight loss, stool consistency and blood in faeces during disease progression was represented, and in b, the changes of colon length during active colitis were given. Each control and experimental group contained a minimum of n = 6 mice.
Fig. 2
Fig. 2
Colon homogenates assessed for a PHD-1, b PHD-2 and c PHD-3 protein levels. Each control and experimental group contained a minimum of n = 6 mice. PHD-1 level was found to be increased with disease progression in murine model of colitis.
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