Mutation in the human gene and protein database mutation, gene that encodes the 15-hydroxyprostaglandin dehydrogenase
, a key enzyme responsible for the degradation of prostaglandins, leads to high levels of PGs, especially PGE2 and excessive formation of collagen by fibroblast hyper activation.
However, paricalcitol did not affect the mRNA levels of prostaglandin E synthases (PGES), the enzyme that isomerizes the [PGH.sub.2] to [PGE.sub.2], or 15-hydroxyprostaglandin dehydrogenase
(15-PGDH), the enzyme that catalyzes conversion of [PGE.sub.2] to a less bioactive form (Figure 1(b)).
The researchers found that individuals whose colons had high levels of a specific gene product, 15-hydroxyprostaglandin dehydrogenase
(15-PGDH) RNA, dramatically reduce their chances of developing colorectal cancer by taking aspirin, while analgesic provided no benefit to individuals whose colons showed low levels of 15-PGDH.
Choi et al., "Synthesis and biological evaluation of novel thiazolidinedione analogues as 15-hydroxyprostaglandin dehydrogenase
inhibitors," Journal of Medicinal Chemistry, vol.
(4) Homozygous mutations in the 15-hydroxyprostaglandin dehydrogenase (HPDG) result in an elevated prostaglandin E2 level, which has been suggested as a pathogenesis of PDP.
Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy.