Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis.

Bakshi, HA; Mishra, V; Satija, S; Mehta, M; Hakkim, FL; Kesharwani, P; Dua, K; Chellappan, DK; Charbe, NB; Shrivastava, G; Rajeshkumar, S; Aljabali, AA; Al-Trad, B; Pabreja, K; Tambuwala, MM

Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis.

Bakshi, HA Mishra, V Satija, S

Mehta, M Hakkim, FL Kesharwani, P Dua, K

Chellappan, DK Charbe, NB Shrivastava, G Rajeshkumar, S Aljabali, AA Al-Trad, B Pabreja, K Tambuwala, MM

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Publisher:: SPRINGER/PLENUM PUBLISHERS
Publication Type:: Journal Article
Citation:: Inflammation, 2019, 42, (6), pp. 2032-2036
Issue Date:: 2019-12

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Field	Value	Language
dc.contributor.author	Bakshi, HA
dc.contributor.author	Mishra, V
dc.contributor.author	Satija, S https://orcid.org/0000-0003-4702-6534
dc.contributor.author	Mehta, M
dc.contributor.author	Hakkim, FL
dc.contributor.author	Kesharwani, P
dc.contributor.author	Dua, K https://orcid.org/0000-0002-7507-1159
dc.contributor.author	Chellappan, DK
dc.contributor.author	Charbe, NB
dc.contributor.author	Shrivastava, G
dc.contributor.author	Rajeshkumar, S
dc.contributor.author	Aljabali, AA
dc.contributor.author	Al-Trad, B
dc.contributor.author	Pabreja, K
dc.contributor.author	Tambuwala, MM
dc.date.accessioned	2020-05-19T00:47:34Z
dc.date.available	2020-05-19T00:47:34Z
dc.date.issued	2019-12
dc.identifier.citation	Inflammation, 2019, 42, (6), pp. 2032-2036
dc.identifier.issn	0360-3997
dc.identifier.issn	1573-2576
dc.identifier.uri	http://hdl.handle.net/10453/140803
dc.description.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.
dc.format	Print
dc.language	eng
dc.publisher	SPRINGER/PLENUM PUBLISHERS
dc.relation.ispartof	Inflammation
dc.relation.isbasedon	10.1007/s10753-019-01065-3
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Colitis
dc.subject.mesh	Inflammatory Bowel Diseases
dc.subject.mesh	Disease Progression
dc.subject.mesh	Protein Isoforms
dc.subject.mesh	Hypoxia-Inducible Factor-Proline Dioxygenases
dc.subject.mesh	Prolyl-Hydroxylase Inhibitors
dc.subject.mesh	Prolyl Hydroxylases
dc.subject.mesh	Animals
dc.subject.mesh	Colitis
dc.subject.mesh	Disease Progression
dc.subject.mesh	Hypoxia-Inducible Factor-Proline Dioxygenases
dc.subject.mesh	Inflammatory Bowel Diseases
dc.subject.mesh	Mice
dc.subject.mesh	Prolyl Hydroxylases
dc.subject.mesh	Prolyl-Hydroxylase Inhibitors
dc.subject.mesh	Protein Isoforms
dc.title	Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis.
dc.type	Journal Article
utslib.citation.volume	42
utslib.location.activity	United States
utslib.for	1107 Immunology
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
dc.date.updated	2020-05-19T00:47:28Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	42
utslib.start-page	2032
utslib.citation.issue	6

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.

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http://hdl.handle.net/10453/140803