TY - JOUR
T1 - Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis
AU - Bakshi, Hamid A.
AU - Mishra, Vijay
AU - Satija, Saurabh
AU - Mehta, Meenu
AU - Hakkim, Faruk L.
AU - Kesharwani, Prashant
AU - Dua, Kamal
AU - Chellappan, Dinesh K.
AU - Charbe, Nitin B.
AU - Shrivastava, Garima
AU - Rajeshkumar, S.
AU - Aljabali, Alaa A.
AU - Al-trad, Bahaa
AU - Pabreja, Kavita
AU - Tambuwala, Murtaza M.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - colitis
KW - Prolyl hydroxylase
KW - In vivo
KW - prolyl hydroxylases
KW - disease activity index
KW - inflammatory bowel disease
UR - https://link.springer.com/article/10.1007/s10753-019-01065-3
UR - https://www.ncbi.nlm.nih.gov/pubmed/31377947
UR - http://www.scopus.com/inward/record.url?scp=85073683482&partnerID=8YFLogxK
U2 - 10.1007/s10753-019-01065-3
DO - 10.1007/s10753-019-01065-3
M3 - Article
C2 - 31377947
SN - 1573-2576
VL - 42
SP - 2032
EP - 2036
JO - Inflammation
JF - Inflammation
IS - 6
ER -
